Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Subramanian A, Shu-Uin G, Kae-Siang N, Gauthaman K, Biswas A, Choolani M, Bongso A, Chui-Yee F. Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J Cell Biochem 2012;113:1886-95. [PMID: 22234854 DOI: 10.1002/jcb.24057] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

For:	Subramanian A, Shu-Uin G, Kae-Siang N, Gauthaman K, Biswas A, Choolani M, Bongso A, Chui-Yee F. Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J Cell Biochem 2012;113:1886-95. [PMID: 22234854 DOI: 10.1002/jcb.24057] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Number

Cited by Other Article(s)

Li X, Zhang F, Sun L, Cai X, Lou F, Sun Y, Gao M, Wang Z, Tang S, Fan L, Wu Y, Jin X, Deng S, Xu Z, Sun X, Li Q, Wang H. Single-Cell RNA Sequencing Identifies WARS1+ Mesenchymal Stem Cells with Enhanced Immunomodulatory Capacity and Improved Therapeutic Efficacy. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2024;213:257-267. [PMID: 38856632 DOI: 10.4049/jimmunol.2300752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/26/2024] [Indexed: 06/11/2024]

Affiliation(s)

Xiangxiao Li Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Fengjiao Zhang Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Libo Sun Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xiaojie Cai Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Fangzhou Lou Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yang Sun Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Min Gao Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhikai Wang Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Sibei Tang Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Li Fan Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yue Wu Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xinping Jin Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Siyu Deng Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhenyao Xu Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xuxu Sun Department of Biochemistry and Molecular Cell Biology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Qun Li Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Honglin Wang Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Chin SP, Marzuki M, Tai L, Mohamed Shahrehan NA, Ricky C, Fanty A, Salleh A, Low CT, Then KY, Hoe SLL, Cheong SK. Dynamic tracking of human umbilical cord mesenchymal stem cells (hUC-MSCs) following intravenous administration in mice model. Regen Ther 2024;25:273-283. [PMID: 38314402 PMCID: PMC10834363 DOI: 10.1016/j.reth.2024.01.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/07/2024] [Accepted: 01/18/2024] [Indexed: 02/06/2024] Open

Arte PA, Tungare K, Bhori M, Jobby R, Aich J. Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach. Hum Cell 2024;37:54-84. [PMID: 38038863 DOI: 10.1007/s13577-023-01007-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023]

Jahani S, Zare N, Mirzaei Y, Arefnezhad R, Zarei H, Goleij P, Bagheri N. Mesenchymal stem cells and ovarian cancer: Is there promising news? J Cell Biochem 2023;124:1437-1448. [PMID: 37682985 DOI: 10.1002/jcb.30471] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/24/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023]

Rebelatto CLK, Boldrini-Leite LM, Daga DR, Marsaro DB, Vaz IM, Jamur VR, de Aguiar AM, Vieira TB, Furman BP, Aguiar CO, Brofman PRS. Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development. Int J Mol Sci 2023;24:12955. [PMID: 37629136 PMCID: PMC10455270 DOI: 10.3390/ijms241612955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/09/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open

Affiliation(s)

Carmen Lúcia Kuniyoshi Rebelatto Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Lidiane Maria Boldrini-Leite Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Debora Regina Daga Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Daniela Boscaro Marsaro Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Isadora May Vaz Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Valderez Ravaglio Jamur Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
Alessandra Melo de Aguiar Laboratory of Basic Biology of Stem Cells, Carlos Chagas Institute—Fiocruz-Paraná, Curitiba 81350-010, Brazil;
Thalita Bastida Vieira Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
Bianca Polak Furman Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
Cecília Oliveira Aguiar Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
Paulo Roberto Slud Brofman Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.) National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil

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Wan W, Miao Y, Niu Y, Zhu K, Ma Y, Pan M, Ma B, Wei Q. Human umbilical cord mesenchymal stem cells conditioned medium exerts anti-tumor effects on KGN cells in a cell density-dependent manner through activation of the Hippo pathway. Stem Cell Res Ther 2023;14:46. [PMID: 36941685 PMCID: PMC10029233 DOI: 10.1186/s13287-023-03273-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open

Abstract

BACKGROUND

The conditioned medium from human umbilical cord mesenchymal stem cells (UCMSCs-CM) provides a new cell-free therapy for tumors due to its unique secretome. However, there are many contradictory reports about the effect of UCMSCs-CM on tumor cells. The loss of contact inhibition is a common characteristic of tumor cells. A relationship between the effect of UCMSCs-CM on tumor cells and contact inhibition in tumor cells is rarely concerned. Whether the effect of UCMSCs-CM on tumor cells is affected by cell density? Here, we explored the effect of UCMSCs-CM on granulosa tumor cell line (KGN) cells at low or high density.

METHODS

Growth curve and CCK8 assay were used to assess cell proliferation and viability. Scratch wound and matrigel invasion assay were implicated to detect cell motility of KGN cells. UCMSCs-CM effects on cell cycle, apoptosis and pathway-related proteins were investigated by flow cytometry, TUNEL assay, western blot and immunofluorescence analysis respectively.

RESULTS

In growth curve analysis, before KGN cells proliferated into confluence, UCMSCs-CM had no effect on cell proliferation. However, once the cells proliferate to contact each other, UCMSCs-CM significantly inhibited proliferation. Meanwhile, when KGN cells were implanted at high density, UCMSCs-CM could induce cell cycle arrest at G1 phase, inhibit cell migration, invasion and promote apoptosis. While it had no similar effect on KGN cells implanted at low density. In mechanism, the UCMSCs-CM treatment activated the Hippo pathway when KGN cells were implanted at high density. Consistently, the MST1/2 inhibitor, XMU-MP-1, inhibited the activation of the Hippo pathway induced by UCMSCs-CM treatment and accordingly declined the anti-tumor effect of UCMSCs-CM on KGN cells.

CONCLUSIONS

The effect of UCMSCs-CM on tumor cells is affected by cell density. UCMSCs-CM exerted anti-tumor effect on KGN cells by activating Hippo pathway to restore contact inhibition. Our results suggest that UCMSCs-CM is a promising therapeutic candidate for GCT treatment.

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Affiliation(s)

Wenjing Wan Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Yuyang Miao Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Yuwei Niu Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Kunyuan Zhu Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Yingwan Ma Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Menghao Pan Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China
Baohua Ma Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China. College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China.
Qiang Wei Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling, 712100, Shaanxi, China. College of Veterinary Medicine, Northwest A and F University, Yangling, 712100, Shaanxi, China.

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Abolghasemi R, Ebrahimi-Barough S, Mohamadnia A, Ai J. Synergistic inhibitory effect of human umbilical cord matrix mesenchymal stem cells-conditioned medium and atorvastatin on MCF7 cancer cells viability and migration. Cell Tissue Bank 2022;23:767-789. [PMID: 34988840 PMCID: PMC8730305 DOI: 10.1007/s10561-021-09984-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/28/2021] [Indexed: 11/27/2022]

Abstract

Recent studies have demonstrated inhibitory effects of mesenchymal stem cells on breast tumors. Likewise, the emerging interest in statins as anticancer agents is based on their pleiotropic effects. In the present study, we investigated whether atorvastatin and umbilical cord matrix derived mesenchymal stem cells-conditioned medium affect the MCF7 cancer cells viability and interactions. We measured the viability of MCF7 cancer cells by MTT assay, flow cytometry, and quantitative real-time PCR. Two-dimensional culture and hanging drop aggregation assay illustrated the morphological changes. We traced the MCF7 migration via scratch-wound healing test and trans-well assay. The results showed the inhibition of cancer cell viability in all treated groups compared to the control group. The effect of atorvastatin and conditioned medium combination was significantly more than each substance separately. The morphological changes indicated apoptosis in treated cells. The annexin V/PI flow cytometry especially in the combination-treated group displayed decreasing in DNA synthesis and cell cycle arrest in G1 and G2/M phases. As well, the mRNA expressions of caspases 3, 8, 9, and Bcl-2 genes were along with extrinsic and intrinsic apoptosis pathways. Conditioned medium disrupted the connections between cancer cells, so the spheroids in three-dimensional configuration lost their order and dispersed. The migration of treated cells across the wound area and trans-well diminished, particularly by the conditioned medium and atorvastatin combination. There fore, the synergistic anti-proliferative and anti-motility effect of atorvastatin along with human umbilical cord mesenchymal stem cells-derived conditioned medium on MCF7 breast cancer cells have been proved. The results might lead the development of novel adjuvant anticancer therapeutics based on targeting or modifying the extracellular matrix to increase chemotherapy results or to prevent metastatic colonization. Schematic representation of "Synergistic Inhibitory Effect of Human Umbilical Cord Matrix Mesenchymal Stem Cells-Conditioned Medium and Atorvastatin on MCF7 Cancer Cells Viablity and Migration" by: Dr. Reyhaneh Abolghasemi, Dr. Somayeh Ebrahimi-barough, Proffesor. Jafar Ai.

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Silini AR, Ramuta TŽ, Pires AS, Banerjee A, Dubus M, Gindraux F, Kerdjoudj H, Maciulatis J, Weidinger A, Wolbank S, Eissner G, Giebel B, Pozzobon M, Parolini O, Kreft ME. Methods and criteria for validating the multimodal functions of perinatal derivatives when used in oncological and antimicrobial applications. Front Bioeng Biotechnol 2022;10:958669. [PMID: 36312547 PMCID: PMC9607958 DOI: 10.3389/fbioe.2022.958669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/26/2022] [Indexed: 11/18/2022] Open

Affiliation(s)

Antonietta R. Silini Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
Taja Železnik Ramuta Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Ljubljana, Slovenia
Ana Salomé Pires Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Institute of Biophysics, University of Coimbra, Coimbra, Portugal Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
Asmita Banerjee Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Vienna, Austria
Marie Dubus Université de Reims Champagne Ardenne, EA 4691 Biomatériaux et Inflammation en Site Osseux (BIOS), Reims, France
Florelle Gindraux Service de Chirurgie Orthopédique, Traumatologique et Plastique, CHU Besançon and Laboratoire de Nanomédecine, Imagerie, Thérapeutique EA 4662, Université Bourgogne Franche-Comté, Besançon, France
Halima Kerdjoudj Université de Reims Champagne Ardenne, EA 4691 Biomatériaux et Inflammation en Site Osseux (BIOS), Reims, France
Justinas Maciulatis The Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
Adelheid Weidinger Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Vienna, Austria
Susanne Wolbank Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Vienna, Austria
Günther Eissner Systems Biology Ireland, UCD School of Medicine, University College Dublin, Dublin, Ireland
Bernd Giebel Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Michela Pozzobon Stem Cells and Regenerative Medicine Lab, Department of Women’s and Children’s Health, University of Padova, Fondazione Istituto di Ricerca Pediatrica Città Della Speranza, Padoa, Italy
Ornella Parolini Department of Life Science and Public Health, Università Cattolica Del Sacro Cuore, Rome, Italy Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
Mateja Erdani Kreft Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Ljubljana, Slovenia *Correspondence: Mateja Erdani Kreft,

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Serras AS, Camões SP, Antunes B, Costa VM, Dionísio F, Yazar V, Vitorino R, Remião F, Castro M, Oliveira NG, Miranda JP. The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells. Int J Mol Sci 2021;22:ijms222313072. [PMID: 34884877 PMCID: PMC8657836 DOI: 10.3390/ijms222313072] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/23/2021] [Accepted: 11/28/2021] [Indexed: 12/20/2022] Open

Affiliation(s)

Ana S. Serras Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.)
Sérgio P. Camões Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.)
Bernardo Antunes Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.)
Vera M. Costa Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; (V.M.C.); (F.D.); (F.R.) UCIBIO—Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Flávio Dionísio Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; (V.M.C.); (F.D.); (F.R.) UCIBIO—Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Volkan Yazar Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA;
Rui Vitorino LAQV-REQUIMTE, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; Cardiovascular R&D Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Oporto, Portugal iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
Fernando Remião Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; (V.M.C.); (F.D.); (F.R.) UCIBIO—Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Matilde Castro Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.)
Nuno G. Oliveira Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.)
Joana P. Miranda Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal; (A.S.S.); (S.P.C.); (B.A.); (M.C.); (N.G.O.) Correspondence:

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Zhao L, Zhang K, He H, Yang Y, Li W, Liu T, Li J. The Relationship Between Mesenchymal Stem Cells and Tumor Dormancy. Front Cell Dev Biol 2021;9:731393. [PMID: 34712663 PMCID: PMC8545891 DOI: 10.3389/fcell.2021.731393] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 09/13/2021] [Indexed: 12/12/2022] Open

Strategies to Improve the Efficiency of Transplantation with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke: A Review of Recent Progress. Stem Cells Int 2021;2021:9929128. [PMID: 34490053 PMCID: PMC8418553 DOI: 10.1155/2021/9929128] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 12/11/2022] Open

Abstract

Cerebral ischemia is a common global disease that is characterized by a loss of neurological function and a poor prognosis in many patients. However, only a limited number of treatments are available for this condition at present. Given that the efficacies of these treatments tend to be poor, cerebral ischemia can create a significant burden on patients, families, and society. Mesenchymal stem cell (MSC) transplantation treatment has shown significant potential in animal models of ischemic stroke; however, the specific mechanisms underlying this effect have yet to be elucidated. Furthermore, clinical trials have yet to yield promising results. Consequently, there is an urgent need to identify new methods to improve the efficiency of MSC transplantation as an optimal treatment for ischemic stroke. In this review, we provide an overview of recent scientific reports concerning novel strategies that promote MSC transplantation as an effective therapeutic approach, including physical approaches, chemical agents, traditional Chinese medicines and extracts, and genetic modification. Our analyses showed that two key factors need to be considered if we are to improve the efficacy of MSC transplantation treatments: survival ability and homing ability. We also highlight the importance of other significant mechanisms, including the enhanced activation of MSCs to promote neurogenesis and angiogenesis, and the regulation of permeability in the blood-brain barrier. Further in-depth investigations of the specific mechanisms underlying MSC transplantation treatment will help us to identify effective methods that improve the efficiency of MSC transplantation for ischemic stroke. The development of safer and more effective methods will facilitate the application of MSC transplantation as a promising adjuvant therapy for the treatment of poststroke brain damage.

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Liang YH, Wu JM, Teng JW, Hung E, Wang HS. Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells. Sci Rep 2021;11:14720. [PMID: 34282169 PMCID: PMC8289868 DOI: 10.1038/s41598-021-94006-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 07/05/2021] [Indexed: 11/09/2022] Open

Shokati A, Naser Moghadasi A, Nikbakht M, Sahraian MA, Mousavi SA, Ai J. A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis. Stem Cell Res Ther 2021;12:400. [PMID: 34256857 PMCID: PMC8278627 DOI: 10.1186/s13287-021-02477-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 06/13/2021] [Indexed: 12/23/2022] Open

Mansouri V, Beheshtizadeh N, Gharibshahian M, Sabouri L, Varzandeh M, Rezaei N. Recent advances in regenerative medicine strategies for cancer treatment. Biomed Pharmacother 2021;141:111875. [PMID: 34229250 DOI: 10.1016/j.biopha.2021.111875] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/23/2021] [Accepted: 06/28/2021] [Indexed: 02/07/2023] Open

Rahmani-Moghadam E, Zarrin V, Mahmoodzadeh A, Owrang M, Talaei-Khozani T. Comparison of the Characteristics of Breast Milk-derived Stem Cells with the Stem Cells Derived from the Other Sources: A Comparative Review. Curr Stem Cell Res Ther 2021;17:71-90. [PMID: 34161214 DOI: 10.2174/1574888x16666210622125309] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/14/2021] [Accepted: 03/28/2021] [Indexed: 11/22/2022]

Li C, Mills Z, Zheng Z. Novel cell sources for bone regeneration. MedComm (Beijing) 2021;2:145-174. [PMID: 34766140 PMCID: PMC8491221 DOI: 10.1002/mco2.51] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 12/03/2020] [Accepted: 12/09/2020] [Indexed: 01/09/2023] Open

Bolli R, Solankhi M, Tang XL, Kahlon A. Cell Therapy in Patients with Heart Failure: A Comprehensive Review and Emerging Concepts. Cardiovasc Res 2021;118:951-976. [PMID: 33871588 PMCID: PMC8930075 DOI: 10.1093/cvr/cvab135] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 04/15/2021] [Indexed: 12/16/2022] Open

Lin HD, Fong CY, Biswas A, Bongso A. Allogeneic human umbilical cord Wharton's jelly stem cells increase several-fold the expansion of human cord blood CD34+ cells both in vitro and in vivo. Stem Cell Res Ther 2020;11:527. [PMID: 33298170 PMCID: PMC7724853 DOI: 10.1186/s13287-020-02048-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open

Abstract

Background

The transplantation of human umbilical cord blood (UCB) CD34+ cells has been successfully used to treat hematological disorders but one major limitation has been the low cell numbers available. Mesenchymal stem cells (MSCs) lying within the bone marrow in vivo behave like a scaffold on which CD34+ cells interact and proliferate. We therefore evaluated the use of allogeneic MSCs from the human UC Wharton’s jelly (hWJSCs) as stromal support for the ex vivo expansion of CD34+ cells.

Methods

We performed an in-depth evaluation of the primitiveness, migration, adhesion, maturation, mitochondrial behavior, and pathway mechanisms of this platform using conventional assays followed by the evaluation of engraftment potential of the expanded CD34+ cells in an in vivo murine model.

Results

We demonstrate that hWJSCs and its conditioned medium (hWJSC-CM) support the production of significantly high fold changes of CD34+, CD34+CD133+, CD34+CD90+, CD34+ALDH+, CD34+CD45+, and CD34+CD49f+ cells after 7 days of interaction when compared to controls. In the presence of hWJSCs or hWJSC-CM, the CD34+ cells produced significantly more primitive CFU-GEMM colonies, HoxB4, and HoxA9 gene expression and lower percentages of CD34+CXCR4+ cells. There were also significantly higher N-cadherin+ cell numbers and increased cell migration in transwell migration assays. The CD34+ cells expanded with hWJSCs had significantly lower mitochondrial mass, mitochondrial membrane potential, and oxidative stress. Green Mitotracker-tagged mitochondria from CD34+ cells were observed lying within red CellTracker-tagged hWJSCs under confocal microscopy indicating mitochondrial transfer via tunneling nanotubes. CD34+ cells expanded with hWJSCs and hWJSC-CM showed significantly reduced oxidative phosphorylation (ATP6VIH and NDUFA10) and increased glycolytic (HIF-1a and HK-1) pathway-related gene expression. CD34+ cells expanded with hWJSCs for 7 days showed significant greater CD45+ cell chimerism in the bone marrow of primary and secondary irradiated mice when transplanted intravenously.

Conclusions

In this report, we confirmed that allogeneic hWJSCs provide an attractive platform for the ex vivo expansion of high fold numbers of UCB CD34+ cells while keeping them primitive. Allogeneic hWJSCs are readily available in abundance from discarded UCs, can be easily frozen in cord blood banks, thawed, and then used as a platform for UCB-HSC expansion if numbers are inadequate.

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Qiu Y, Sun J, Qiu J, Chen G, Wang X, Mu Y, Li K, Wang W. Antitumor Activity of Cabazitaxel and MSC-TRAIL Derived Extracellular Vesicles in Drug-Resistant Oral Squamous Cell Carcinoma. Cancer Manag Res 2020;12:10809-10820. [PMID: 33149686 PMCID: PMC7605918 DOI: 10.2147/cmar.s277324] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 10/03/2020] [Indexed: 12/19/2022] Open

Abstract

INTRODUCTION

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can induce apoptosis in a variety of cancer cells. However, drug resistance of tumor and short half-life seriously affects its clinical targeted therapy. Cabazitaxel (CTX) is a taxane drug, which can induce apoptosis or autophagy by inhibiting the phosphorylation of PI3K/Akt/mTOR and sensitive to some drug-resistant tumors. Therefore, we explored the possibility of developing a mesenchymal stem cell-derived exosomes (MSC-EXO) vector for oral squamous cell carcinoma (OSCC) to deliver CTX/TRAIL combinations.

METHODS

After ultracentrifugation and dialysis, CTX/TRAIL loaded exosomes transfected MSC (MSCT)-derived exosome (EXO) (MSCT-EXO/CTX) were isolated and purified. The expression of CD63, CD9 and TRAIL was detected by BCA to confirm the origin of EXO. High-performance liquid chromatography (HPLC) was used to determine the drug loading of VPF and draw the in vitro release profile. MTT assay, flow cytometry and Western blot were used to detect the antitumor effect of MSCT-EXO/CTX in vitro. Subsequently, the antitumor effect of MSCT-EXO/CTX in vivo was verified by mouse model.

RESULTS

The diameter of the membrane particles was about 60-150 nm. We have proved that the incorporation and release of CTX in MSCT-EXO can inhibit the activation of PI3K, Akt and mTOR, which is a possible synergistic mechanism of CTX. MSCT-EXO and CTX can induce the apoptosis of SCC25 tumor cells in a dose-dependent manner and exert a good synergistic effect in the proportion range of 10:1-5:1. The inherent activity of MSCT-EXO and the direct effect of MSCT-EXO/CTX on OSCC confirm that MSCT-EXO/CTX makes MSCT-EXO and CTX have an efficient synergistic effect and a highly effective pharmacological inhibition on cancer cells, as verified by the subsequent mouse model. MSCT-EXO/CTX showed the lowest relative tumor volume and the highest tumor inhibition rate (P<0.05) in vivo.

CONCLUSION

An MSCT-EXO-based CTX delivery system might be an effective anticancer method.

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E LL, Cheng T, Li CJ, Zhang R, Zhang S, Liu HC, Zheng WJ. Combined Use of Recombinant Human BMP-7 and Osteogenic Media May Have No Ideal Synergistic Effect on Leporine Bone Regeneration of Human Umbilical Cord Mesenchymal Stem Cells Seeded on Nanohydroxyapatite/Collagen/Poly (l-Lactide). Stem Cells Dev 2020;29:1215-1228. [PMID: 32674666 DOI: 10.1089/scd.2020.0066] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Abstract

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising alternative source of mesenchymal stem cells (MSCs) that are enormously attractive for clinical use. This study was designed to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) and/or osteogenic media (OMD) on bone regeneration of hUC-MSCs seeded on nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA) in a rabbit model. The characteristics of stem cells were analyzed by plastic adherence, cell phenotype, and multilineage differentiation potential. Cell proliferation was examined using cell counting kit-8 assay. Osteogenic differentiation was evaluated by quantitative Ca²⁺ concentration, PO₄^3- concentration, alkaline phosphatase (ALP) activity, osteocalcin (OCN) secretion, and mineralized matrix formation. Bone regeneration was investigated in jaw bone defect repair in rabbit by microcomputed tomography, fluorescent labeling, and hematoxylin and eosin staining. Except for initial stress response, OMD and OMD + rhBMP-7 inhibited the proliferation of hUC-MSCs seeded on nHAC/PLA; rhBMP-7 inhibited cell proliferation in the nonlogarithmic phase and attenuated the inhibitory effect of OMD on cell proliferation. The inhibitory effects of OMD, rhBMP-7, and OMD + rhBMP-7 on cell proliferation were ranked as OMD > OMD + rhBMP-7 > rhBMP-7. OMD, rhBMP-7, and OMD + rhBMP-7 promoted Ca²⁺ concentration, PO₄^3- concentration, ALP activity, OCN secretion, and mineralized matrix formation of hUC-MSCs seeded on nHAC/PLA. The promoting effects of OMD, rhBMP-7, and OMD+rhBMP-7 on Ca²⁺ concentration, PO₄^3- concentration, ALP activity, OCN secretion, and mineralized matrix formation were ranked as rhBMP-7 > OMD > OMD + rhBMP-7, OMD > OMD + rhBMP-7 > rhBMP-7, OMD > rhBMP-7 > OMD + rhBMP-7, rhBMP-7 > OMD + rhBMP-7 > OMD, and OMD > rhBMP-7 > OMD + rhBMP-7, respectively. In rabbit jaw bone defect repair, OMD, rhBMP-7, and OMD + rhBMP-7 enhanced bone regeneration of hUC-MSCs seeded on nHAC/PLA, but the largest bone mineral apposition rate and bone formation were presented in cultures with rhBMP-7. These findings suggested that the combined use of rhBMP-7 and OMD may have no ideal synergistic effect on bone regeneration of hUC-MSCs seeded on nHAC/PLA in rabbit jaw bone defect.

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Lu Z, Zhu L, Liu Z, Wu J, Xu Y, Zhang CJ. IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year Follow-Up Study. Front Neurol 2020;11:967. [PMID: 33013641 PMCID: PMC7506071 DOI: 10.3389/fneur.2020.00967] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 07/24/2020] [Indexed: 12/28/2022] Open

Affiliation(s)

Zhengjuan Lu Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China
Lin Zhu Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China
Zhuo Liu Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China
Jiayong Wu Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China
Yun Xu Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China
Cun-Jin Zhang Department of Neurology of Nanjing Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.,Department of Neurology, Institute of Brain Sciences, Nanjing University, Nanjing, China.,Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.,Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China.,Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China

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Song JS, Hong KT, Kong CG, Kim NM, Jung JY, Park HS, Kim YJ, Chang KB, Kim SJ. High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration. World J Stem Cells 2020;12:514-526. [PMID: 32742568 PMCID: PMC7360989 DOI: 10.4252/wjsc.v12.i6.514] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/24/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023] Open

Abstract

BACKGROUND

High tibial osteotomy (HTO) is a well-established method for the treatment of medial compartment osteoarthritis of the knee with varus deformity. However, HTO alone cannot adequately repair the arthritic joint, necessitating cartilage regeneration therapy. Cartilage regeneration procedures with concomitant HTO are used to improve the clinical outcome in patients with varus deformity.

AIM

To evaluate cartilage regeneration after implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with concomitant HTO.

METHODS

Data for patients who underwent implantation of hUCB-MSCs with concomitant HTO were evaluated. The patients included in this study were over 40 years old, had a varus deformity of more than 5°, and a full-thickness International Cartilage Repair Society (ICRS) grade IV articular cartilage lesion of more than 4 cm² in the medial compartment of the knee. All patients underwent second-look arthroscopy during hardware removal. Cartilage regeneration was evaluated macroscopically using the ICRS grading system in second-look arthroscopy. We also assessed the effects of patient characteristics, such as trochlear lesions, age, and lesion size, using patient medical records.

RESULTS

A total of 125 patients were included in the study, with an average age of 58.3 ± 6.8 years (range: 43-74 years old); 95 (76%) were female and 30 (24%) were male. The average hip-knee-ankle (HKA) angle for measuring varus deformity was 7.6° ± 2.4° (range: 5.0-14.2°). In second-look arthroscopy, the status of medial femoral condyle (MFC) cartilage was as follows: 73 (58.4%) patients with ICRS grade I, 37 (29.6%) with ICRS grade II, and 15 (12%) with ICRS grade III. No patients were staged with ICRS grade IV. Additionally, the scores [except International Knee Documentation Committee (IKDC) at 1 year] of the ICRS grade I group improved more significantly than those of the ICRS grade II and III groups.

CONCLUSION

Implantation of hUCB-MSCs with concomitant HTO is an effective treatment for patients with medial compartment osteoarthritis and varus deformity. Regeneration of cartilage improves the clinical outcomes for the patients.

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Dong Y, Sun X, Zhang Z, Liu Y, Zhang L, Zhang X, Huang Y, Zhao Y, Qi C, Midgley AC, Wang S, Yang Q. Regional and sustained dual-release of growth factors from biomimetic tri-layered scaffolds for the repair of large-scale osteochondral defects. APPLIED MATERIALS TODAY 2020;19:100548. [DOI: 10.1016/j.apmt.2019.100548] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2025]

Bonsack B, Corey S, Shear A, Heyck M, Cozene B, Sadanandan N, Zhang H, Gonzales-Portillo B, Sheyner M, Borlongan CV. Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury. CNS Neurosci Ther 2020;26:603-615. [PMID: 32356605 PMCID: PMC7248547 DOI: 10.1111/cns.13378] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/28/2020] [Accepted: 03/29/2020] [Indexed: 01/01/2023] Open

Hypoxic Wharton's Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells. Stem Cells Int 2020;2020:4670948. [PMID: 32377203 PMCID: PMC7189315 DOI: 10.1155/2020/4670948] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/03/2020] [Accepted: 03/16/2020] [Indexed: 12/22/2022] Open

Corey S, Bonsack B, Heyck M, Shear A, Sadanandan N, Zhang H, Borlongan CV. Harnessing the anti-inflammatory properties of stem cells for transplant therapy in hemorrhagic stroke. BRAIN HEMORRHAGES 2020;1:24-33. [PMID: 34056567 PMCID: PMC8158660 DOI: 10.1016/j.hest.2019.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

Ai J, Ketabchi N, Verdi J, Gheibi N, Khadem Haghighian H, Kavianpour M. Mesenchymal stromal cells induce inhibitory effects on hepatocellular carcinoma through various signaling pathways. Cancer Cell Int 2019;19:329. [PMID: 31827403 PMCID: PMC6894473 DOI: 10.1186/s12935-019-1038-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/16/2019] [Indexed: 12/13/2022] Open

Moquin-Beaudry G, Colas C, Li Y, Bazin R, Guimond JV, Haddad E, Beauséjour C. The Tumor-Immune Response Is Not Compromised by Mesenchymal Stromal Cells in Humanized Mice. THE JOURNAL OF IMMUNOLOGY 2019;203:2735-2745. [PMID: 31578272 DOI: 10.4049/jimmunol.1900807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 09/10/2019] [Indexed: 12/14/2022]

Colicchia M, Jones DA, Beirne AM, Hussain M, Weeraman D, Rathod K, Veerapen J, Lowdell M, Mathur A. Umbilical cord-derived mesenchymal stromal cells in cardiovascular disease: review of preclinical and clinical data. Cytotherapy 2019;21:1007-1018. [PMID: 31540804 DOI: 10.1016/j.jcyt.2019.04.056] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 04/10/2019] [Accepted: 04/15/2019] [Indexed: 02/07/2023]

Barrett AN, Fong CY, Subramanian A, Liu W, Feng Y, Choolani M, Biswas A, Rajapakse JC, Bongso A. Human Wharton's Jelly Mesenchymal Stem Cells Show Unique Gene Expression Compared with Bone Marrow Mesenchymal Stem Cells Using Single-Cell RNA-Sequencing. Stem Cells Dev 2019;28:196-211. [PMID: 30484393 DOI: 10.1089/scd.2018.0132] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Abstract

Human Wharton's jelly stem cells (hWJSCs) isolated from the human umbilical cord are a unique population of mesenchymal stem cells (MSCs) with significant clinical utility. Their broad differentiation potential, high rate of proliferation, ready availability from discarded cords, and prolonged maintenance of stemness properties in culture make them an attractive alternative source of MSCs with therapeutic value compared with human bone marrow MSCs (hBMMSCs). We aimed to characterize the differences in gene expression profiles between these two stem cell types using single-cell RNA sequencing (scRNA-Seq) to determine which pathways are involved in conferring hWJSCs with their unique properties. We identified 436 significantly differentially expressed genes between the two cell types, playing roles in processes, including immunomodulation, angiogenesis, wound healing, apoptosis, antitumor activity, and chemotaxis. Expression of immune molecules is particularly high in hWJSCs compared with hBMMSCs. These differences in gene expression may help to explain many of the advantages that hWJSCs have over hBMMSCs for clinical application. Although cell surface protein marker expression indicates that isolated hWJSCs and hBMMSCs are both homogenous populations, using scRNA-Seq we can clearly identify extreme variability in expression levels between individual cells within a certain cell type. If the cells are examined as bulk populations, it is not possible to appreciate that a single cell may be making a major unique contribution to the apparent overall expression level. We demonstrated how the fine tuning of expression within hWJSCs and hBMMSCs may be achieved by expression of molecules with opposing function between two cells. We hypothesize that a greater understanding of these differences in gene expression between the two cell types may aid in the development of new therapies using hWJSCs.

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Peng C, Zou X, Xia W, Gao H, Li Z, Liu N, Xu Z, Gao C, He Z, Niu W, Fang R, Biswas S, Agrez M, Zhi X, Niu J. Integrin αvβ6 plays a bi-directional regulation role between colon cancer cells and cancer-associated fibroblasts. Biosci Rep 2018;38:BSR20180243. [PMID: 30355650 PMCID: PMC6435516 DOI: 10.1042/bsr20180243] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 09/20/2018] [Accepted: 10/09/2018] [Indexed: 12/11/2022] Open

Affiliation(s)

Cheng Peng Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Xueqing Zou Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Wanying Xia Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China
Huijie Gao Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Zequn Li Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Naiqing Liu The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China Department of General Surgery, Linyi Central Hospital, Linyi, Shandong, China
Zongquan Xu Department of General Surgery, Jiangxi Provincial Tumor Hospital, Nanchang, Jiangxi, China
Chao Gao Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Zhaobin He Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Weibo Niu Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Ruliang Fang Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China The Institute of Laparoscopic Minimally Invasive Surgery of Shandong University, Shandong University, Jinan, Shandong, China
Siddhartha Biswas Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China
Michael Agrez Newcastle Bowel Cancer Research Collaborative, The University of Newcastle, Callaghan, New South Wales, Australia
Xuting Zhi Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China
Jun Niu Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China

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Secretomes from Mesenchymal Stem Cells against Acute Kidney Injury: Possible Heterogeneity. Stem Cells Int 2018;2018:8693137. [PMID: 30651737 PMCID: PMC6311717 DOI: 10.1155/2018/8693137] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 10/10/2018] [Accepted: 10/24/2018] [Indexed: 12/20/2022] Open

Christodoulou I, Goulielmaki M, Devetzi M, Panagiotidis M, Koliakos G, Zoumpourlis V. Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review. Stem Cell Res Ther 2018;9:336. [PMID: 30526687 PMCID: PMC6286545 DOI: 10.1186/s13287-018-1078-8] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open

Abstract

Mesenchymal stem cells (MSC) comprise a heterogeneous population of rapidly proliferating cells that can be isolated from adult (e.g., bone marrow, adipose tissue) as well as fetal (e.g., umbilical cord) tissues (termed bone marrow (BM)-, adipose tissue (AT)-, and umbilical cord (UC)-MSC, respectively) and are capable of differentiation into a wide range of non-hematopoietic cell types. An additional, unique attribute of MSC is their ability to home to tumor sites and to interact with the local supportive microenvironment which rapidly conceptualized into MSC-based experimental cancer cytotherapy at the turn of the century. Towards this purpose, both naïve (unmodified) and genetically modified MSC (GM-MSC; used as delivery vehicles for the controlled expression and release of antitumorigenic molecules) have been employed using well-established in vitro and in vivo cancer models, albeit with variable success. The first approach is hampered by contradictory findings regarding the effects of naïve MSC of different origins on tumor growth and metastasis, largely attributed to inherent biological heterogeneity of MSC as well as experimental discrepancies. In the second case, although the anti-cancer effect of GM-MSC is markedly improved over that of naïve cells, it is yet apparent that some protocols are more efficient against some types of cancer than others. Regardless, in order to maximize therapeutic consistency and efficacy, a deeper understanding of the complex interaction between MSC and the tumor microenvironment is required, as well as examination of the role of key experimental parameters in shaping the final cytotherapy outcome. This systematic review represents, to the best of our knowledge, the first thorough evaluation of the impact of experimental anti-cancer therapies based on MSC of human origin (with special focus on human BM-/AT-/UC-MSC). Importantly, we dissect the commonalities and differences as well as address the shortcomings of work accumulated over the last two decades and discuss how this information can serve as a guide map for optimal experimental design implementation ultimately aiding the effective transition into clinical trials.

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Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies. Int J Mol Sci 2018;19:ijms19082385. [PMID: 30104541 PMCID: PMC6121292 DOI: 10.3390/ijms19082385] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 08/05/2018] [Accepted: 08/09/2018] [Indexed: 12/13/2022] Open

Yuan Y, Zhou C, Chen X, Tao C, Cheng H, Lu X. Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling. Oncol Lett 2018;15:8536-8544. [PMID: 29805590 PMCID: PMC5950566 DOI: 10.3892/ol.2018.8368] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Accepted: 02/28/2018] [Indexed: 02/07/2023] Open

Medeiros Tavares Marques JC, Cornélio DA, Nogueira Silbiger V, Ducati Luchessi A, de Souza S, Batistuzzo de Medeiros SR. Identification of new genes associated to senescent and tumorigenic phenotypes in mesenchymal stem cells. Sci Rep 2017;7:17837. [PMID: 29259202 PMCID: PMC5736717 DOI: 10.1038/s41598-017-16224-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 11/08/2017] [Indexed: 02/06/2023] Open

Shi Q, Gao J, Jiang Y, Sun B, Lu W, Su M, Xu Y, Yang X, Zhang Y. Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells into endometrial cells. Stem Cell Res Ther 2017;8:246. [PMID: 29096715 PMCID: PMC5667478 DOI: 10.1186/s13287-017-0700-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 10/12/2017] [Accepted: 10/16/2017] [Indexed: 11/10/2022] Open

Abstract

BACKGROUND

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are a novel and promising strategy for tissue engineering because of their ability to differentiate into many cell types. We characterized the differentiation of WJ-MSCs into endometrial epithelial cell (EEC)-like and endometrial stromal cell (ESC)-like cells and assessed the effect of 17β-estradiol and 8-Br-cAMP on the differentiation system.

METHODS

WJ-MSCs were treated in two ways to differentiate into EEC-like and ESC-like cells respectively: cocultured with ESCs in control/differentiation medium (17β-estradiol, growth factors); and cultured in control/differentiation medium (8-Br-cAMP alone or 8-Br-cAMP plus 17β-estrogen and growth factors). Three signaling pathway inhibitors (SB203580, PD98059, H89) were used to investigate the mechanism of WJ-MSC differentiation into ESC-like cells. Immunofluorescence, western blot and flow cytometry analyses were used to analyze expression of epithelial markers and stromal cell markers. Enzyme-linked immunosorbent assays were used to test the production of secretory proteins associated with the differentiation of ESC-like cells.

RESULTS

17β-estradiol at 1 μM downregulated vimentin and CD13 and upregulated cytokeratin and CD9 proteins, promoting the differentiation of WJ-MSCs into EEC-like cells in the coculture system. 8-Br-cAMP at 0.5 mM upregulated vimentin and CD13 and downregulated CK and CD9, promoting the differentiation of WJ-MSCs into ESC-like cells. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) were upregulated and the protein kinase A (PKA) signaling pathway was activated, whereas extracellular signal-regulated (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were not affected.

CONCLUSIONS

17β-estradiol at 1 μM is a good inducer for facilitating the differentiation of WJ-MSCs into EEC-like cells. 8-Br-cAMP plus estrogen and growth factors can induce the differentiation of WJ-MSCs into ESC-like cells. During the differentiation of WJ-MSCs into ESC-like cells, PRL and IGFBP1 were upregulated by the treatment and the PKA signaling pathway was activated, whereas ERK1/2 and p38 MAPK were not affected. These findings suggest a promising approach to the treatment of endometrial damage and other endometrial diseases and suggest new applications for WJ-MSCs in clinical practice.

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Induction of Immunogenic Cell Death in Lymphoma Cells by Wharton’s Jelly Mesenchymal Stem Cell Conditioned Medium. Stem Cell Rev Rep 2017;13:801-816. [DOI: 10.1007/s12015-017-9767-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]

Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms. Prog Neurobiol 2017;158:94-131. [PMID: 28743464 DOI: 10.1016/j.pneurobio.2017.07.004] [Citation(s) in RCA: 188] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 07/18/2017] [Accepted: 07/18/2017] [Indexed: 12/13/2022]

Abstract

Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation. In this review, we investigate clinically relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose tissue-derived stem cells, breast milk-derived stem cells, menstrual blood-derived stem cells, dental tissue-derived stem cells, induced pluripotent stem cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c-mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal cells (SB623), comparing their potential efficacy to sequester stroke-induced neuroinflammation and their feasibility as translational clinical cell sources. To this end, we highlight that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti-inflammatory effects in stroke both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory action against stroke complements the regenerative processes of cell replacement and neurotrophic factor secretion conventionally ascribed to cell-based therapy in neurological disorders.

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Zhang C, Yang SJ, Wen Q, Zhong JF, Chen XL, Stucky A, Press MF, Zhang X. Human-derived normal mesenchymal stem/stromal cells in anticancer therapies. J Cancer 2017;8:85-96. [PMID: 28123601 PMCID: PMC5264043 DOI: 10.7150/jca.16792] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 09/18/2016] [Indexed: 12/14/2022] Open

Affiliation(s)

Cheng Zhang Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.; Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Shi-Jie Yang Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.; Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Qin Wen Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.; Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Jiang F Zhong Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Xue-Lian Chen Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Andres Stucky Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA
Michael F Press Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
Xi Zhang Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.; Division of Periodontology, Diagnostic Sciences & Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.; Norris Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA

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Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence. Stem Cells Int 2016;2016:4798639. [PMID: 27721835 PMCID: PMC5046016 DOI: 10.1155/2016/4798639] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 07/15/2016] [Accepted: 08/18/2016] [Indexed: 12/15/2022] Open

Arutyunyan I, Elchaninov A, Makarov A, Fatkhudinov T. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem Cells Int 2016;2016:6901286. [PMID: 27651799 PMCID: PMC5019943 DOI: 10.1155/2016/6901286] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 07/14/2016] [Indexed: 02/07/2023] Open

Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review. BMC Musculoskelet Disord 2016;17:230. [PMID: 27229856 PMCID: PMC4880954 DOI: 10.1186/s12891-016-1085-9] [Citation(s) in RCA: 194] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 05/17/2016] [Indexed: 01/15/2023] Open

Activation of the Extracellular Signal-Regulated Kinase Signaling Is Critical for Human Umbilical Cord Mesenchymal Stem Cell Osteogenic Differentiation. BIOMED RESEARCH INTERNATIONAL 2016;2016:3764372. [PMID: 26989682 PMCID: PMC4771893 DOI: 10.1155/2016/3764372] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 01/15/2016] [Accepted: 01/21/2016] [Indexed: 01/12/2023]

Lin HD, Fong CY, Biswas A, Choolani M, Bongso A. Human Umbilical Cord Wharton's Jelly Stem Cell Conditioned Medium Induces Tumoricidal Effects on Lymphoma Cells Through Hydrogen Peroxide Mediation. J Cell Biochem 2016;117:2045-55. [PMID: 27392313 DOI: 10.1002/jcb.25501] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 01/26/2016] [Indexed: 12/26/2022]

Abstract

Several groups have reported that human umbilical cord Wharton's jelly stem cells (hWJSCs) possess unique tumoricidal properties against many cancers. However, the exact mechanisms as to how hWJSCs inhibit tumor growth are not known. Recent evidence suggests that exposure of cancer cells to high hydrogen peroxide (H2 O2 ) levels from H2 O2 -releasing drugs causes their death. We therefore explored whether the tumoricidal effect of hWJSCs on lymphoma cells was mediated via H2 O2 . We first exposed lymphoma cells to six different molecular weight cut-off (MWCO) concentrates of hWJSC-conditioned medium (hWJSC-CM) (3, 5, 10, 30, 50, 100 kDa) for 48 h. Since, the 3 kDa-MWCO concentrate showed the greatest cell inhibition we then investigated whether the tumoricidal effect of the specific 3 kDa-MWCO concentrate on two different lymphoma cell lines (Ramos and Toledo) was mediated via accumulation of H2 O2 . We used a battery of assays (MTT, propidium iodide, mitochondria membrane potential, apoptosis, cell cycle, oxidative stress enzymes, hydrogen peroxide, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation) to test this mechanism. The hWJSC-CM-3 kDa MWCO concentrate significantly decreased cell viability and mitochondrial membrane potential and increased cell death and apoptosis in both lymphoma cell lines. There were significant increases in superoxide dismutase with concomitant decreases in glutathione peroxidase, catalase, and thioredoxin peroxidase activities. H2 O2 levels, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation were also significantly increased in both lymphoma cell lines. The results suggested that the hWJSC-CM-3 kDa MWCO concentrate regulates cellular H2 O2 leading to a tumoricidal effect and may thus be a promising anti-lymphoma agent. J. Cell. Biochem. 117: 2045-2055, 2016. © 2016 Wiley Periodicals, Inc.

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Rhee KJ, Lee JI, Eom YW. Mesenchymal Stem Cell-Mediated Effects of Tumor Support or Suppression. Int J Mol Sci 2015;16:30015-33. [PMID: 26694366 PMCID: PMC4691158 DOI: 10.3390/ijms161226215] [Citation(s) in RCA: 162] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/27/2015] [Accepted: 12/01/2015] [Indexed: 02/07/2023] Open

Meng YB, Li X, Li ZY, Zhao J, Yuan XB, Ren Y, Cui ZD, Liu YD, Yang XJ. microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway. J Orthop Res 2015;33:957-64. [PMID: 25728838 DOI: 10.1002/jor.22884] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 02/24/2015] [Indexed: 02/04/2023]

Arutyunyan IV, Makarov AV, Elchaninov AV, Fatkhudinov TK. Umbilical cord-derived multipotent mesenchymal stromal cells: biological properties and clinical applications. GENES & CELLS 2015;10:30-38. [DOI: 10.23868/gc120474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]

Hendijani F. Human mesenchymal stromal cell therapy for prevention and recovery of chemo/radiotherapy adverse reactions. Cytotherapy 2015;17:509-25. [DOI: 10.1016/j.jcyt.2014.10.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 10/07/2014] [Accepted: 10/27/2014] [Indexed: 12/21/2022]

Lin HD, Fong CY, Biswas A, Choolani M, Bongso A. Human Wharton's jelly stem cells, its conditioned medium and cell-free lysate inhibit the growth of human lymphoma cells. Stem Cell Rev Rep 2015;10:573-86. [PMID: 24789672 DOI: 10.1007/s12015-014-9514-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]