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For: Cheng K, Benten D, Bhargava K, Inada M, Joseph B, Palestro C, Gupta S. Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice. Hepatology 2009;50:1194-203. [PMID: 19637284 PMCID: PMC2897246 DOI: 10.1002/hep.23120] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]

For:	Cheng K, Benten D, Bhargava K, Inada M, Joseph B, Palestro C, Gupta S. Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells and adult hepatocytes in mice. Hepatology 2009;50:1194-203. [PMID: 19637284 PMCID: PMC2897246 DOI: 10.1002/hep.23120] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]

Number

Cited by Other Article(s)

Khan S, Khan RS, Newsome PN. Cell Therapy for Liver Disease: From Promise to Reality. Semin Liver Dis 2020;40:411-426. [PMID: 33764490 DOI: 10.1055/s-0040-1717096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Aslam R, Hussain A, Cheng K, Kumar V, Malhotra A, Gupta S, Singhal PC. Transplantation of mesenchymal stem cells preserves podocyte homeostasis through modulation of parietal epithelial cell activation in adriamycin-induced mouse kidney injury model. Histol Histopathol 2020;35:1483-1492. [PMID: 33124682 DOI: 10.14670/hh-18-276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]

Kruitwagen HS, Oosterhoff LA, van Wolferen ME, Chen C, Nantasanti Assawarachan S, Schneeberger K, Kummeling A, van Straten G, Akkerdaas IC, Vinke CR, van Steenbeek FG, van Bruggen LW, Wolfswinkel J, Grinwis GC, Fuchs SA, Gehart H, Geijsen N, Vries RG, Clevers H, Rothuizen J, Schotanus BA, Penning LC, Spee B. Long-Term Survival of Transplanted Autologous Canine Liver Organoids in a COMMD1-Deficient Dog Model of Metabolic Liver Disease. Cells 2020;9:cells9020410. [PMID: 32053895 PMCID: PMC7072637 DOI: 10.3390/cells9020410] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 01/29/2020] [Accepted: 01/30/2020] [Indexed: 12/30/2022] Open

Affiliation(s)

Hedwig S. Kruitwagen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.) Correspondence: (H.S.K.); (B.S.)
Loes A. Oosterhoff Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Monique E. van Wolferen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Chen Chen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Sathidpak Nantasanti Assawarachan Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Kerstin Schneeberger Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Anne Kummeling Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Giora van Straten Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Ies C. Akkerdaas Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Christel R. Vinke Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Frank G. van Steenbeek Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Leonie W.L. van Bruggen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Jeannette Wolfswinkel Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Guy C.M. Grinwis Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands;
Sabine A. Fuchs Division of Pediatric Gastroenterology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands;
Helmuth Gehart Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands; (H.G.); (H.C.)
Niels Geijsen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.) Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands; (H.G.); (H.C.)
Robert G. Vries Hubrecht Organoid Technology (HUB), 3584 CT Utrecht, The Netherlands;
Hans Clevers Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht University, 3584 CT Utrecht, The Netherlands; (H.G.); (H.C.)
Jan Rothuizen Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Baukje A. Schotanus Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Louis C. Penning Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.)
Bart Spee Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; (L.A.O.); (M.E.v.W.); (C.C.); (S.N.A.); (K.S.); (A.K.); (G.v.S.); (I.C.A.); (C.R.V.); (F.G.v.S.); (L.W.L.v.B.); (J.W.); (N.G.); (J.R.); (B.A.S.); (L.C.P.) Correspondence: (H.S.K.); (B.S.)

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Bandi S, Tchaikovskaya T, Gupta S. Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products. Differentiation 2019;105:54-70. [PMID: 30776728 DOI: 10.1016/j.diff.2019.01.005] [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: 09/19/2018] [Revised: 01/22/2019] [Accepted: 01/28/2019] [Indexed: 12/19/2022]

Abstract

Endogenous cell signals regulate tissue homeostasis and are significant for directing the fate of stem cells. During liver development, cytokines released from various cell types are critical for stem/progenitor cell differentiation and lineage expansions. To determine mechanisms in these stage-specific lineage interactions, we modeled potential effects of soluble signals derived from immortalized human fetal liver parenchymal cells on stem cells, including embryonic and induced pluripotent stem cells. For identifying lineage conversion and maturation, we utilized conventional assays of cell morphology, gene expression analysis and lineage markers. Molecular pathway analysis used functional genomics approaches. Metabolic properties were analyzed to determine the extent of hepatic differentiation. Cell transplantation studies were performed in mice with drug-induced acute liver failure to elicit benefits in hepatic support and tissue regeneration. These studies showed signals emanating from fetal liver cells induced hepatic differentiation in stem cells. Gene expression profiling and comparison of regulatory networks in immature and mature hepatocytes revealed stem cell-derived hepatocytes represented early fetal-like stage. Unexpectedly, differentiation-inducing soluble signals constituted metabolomics products and not proteins. In stem cells exposed to signals from fetal cells, mechanistic gene networks of upstream regulators decreased pluripotency, while simultaneously inducing mesenchymal and epithelial properties. The extent of metabolic and synthetic functions in stem cell-derived hepatocytes was sufficient for providing hepatic support along with promotion of tissue repair to rescue mice in acute liver failure. During this rescue, paracrine factors from transplanted cells contributed in stimulating liver regeneration. We concluded that hepatic differentiation of pluripotent stem cells with metabolomics products will be significant for developing therapies. The differentiation mechanisms involving metabolomics products could have an impact on advancing recruitment of stem/progenitor cells during tissue homeostasis.

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Intrasplenic Transplantation of Cytotoxic T-Lymphocyte Associated Protein 4-Fas Ligand--Modified Hepatic Oval Cells for Acute Liver Injury in Rats. Transplant Proc 2019;51:942-950. [PMID: 30979487 DOI: 10.1016/j.transproceed.2019.01.060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 12/19/2018] [Accepted: 01/17/2019] [Indexed: 11/20/2022]

Abstract

BACKGROUND

Intrasplenic transplantation of xenogeneic hepatic oval cells (HOCs) may provide metabolic support for acute liver injury. However, xenoreactive lymphocyte-mediated immune response hinders HOCs' survival in the xeno-spleen parenchyma. Cytotoxic T-lymphocyte associated protein 4-Fas ligand (CTLA4.FasL), a fusion product integrating 2 inhibitory elements against lymphocytes into 1 molecule, effectively inhibited the proliferation of allogeneic and autoimmune lymphocytes. The purpose of this study was to explore the effect of CTLA4.FasL on the proliferation of xenoreactive lymphocytes and evaluate the therapeutic efficacy of CTLA4.FasL-modified HOC transplantation on acute liver injury in rats.

METHODS

The effect of CTLA4.FasL-modified mouse liver epithelial progenitor cells (CTLA4.FasL-LEPCs) on the proliferation of rat lymphocytes in xeno-mixed lymphocyte reaction was investigated. Furthermore, CTLA4.FasL-LEPCs were intrasplenically transplanted in carbon tetrachloride- and partial hepatectomy-treated rats, and the therapeutic effect was evaluated using hematoxylin and eosin staining and alanine aminotransferase and aspartate aminotransferase assays. The hepatocytic differentiation of CTLA4.FasL-LEPCs in xenogeneic spleen was monitored by immunohistochemical staining for albumin.

RESULTS

In xeno-mixed lymphocyte reaction, CTLA4.FasL-LEPCs substantially inhibited the rat lymphocytes proliferation. CTLA4.FasL-LEPC transplantation significantly ameliorated liver injury compared with mCherry-modified LEPC and LEPC transplantation, as assessed by hematoxylin and eosin staining, alanine aminotransferase, and aspartate aminotransferase assays. Albumin positive cells appeared only in CTLA4.FasL-LEPCs group, but not in the mCherry-modified LEPCs group and LEPCs group.

CONCLUSIONS

Our results indicate CTLA4.FasL-LEPCs substantially improved liver function and structure in carbon tetrachloride- and partial hepatectomy-induced acute liver injury rats through long-term hepatocytic differentiation.

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Aimaiti Y, Jin X, Shao Y, Wang W, Li D. Hepatic stellate cells regulate hepatic progenitor cells differentiation via the TGF-β1/Jagged1 signaling axis. J Cell Physiol 2018;234:9283-9296. [PMID: 30317614 DOI: 10.1002/jcp.27609] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 09/21/2018] [Indexed: 12/29/2022]

Abstract

Hepatic stellate cells (HSCs) play an important microenvironmental role in hepatic progenitor cells (HPCs) differentiation fate. To reveal the specific mechanism of HSCs induced by transforming growth factor β1 (TGF-β1) signaling in HPCs differentiation process, we used Knockin and knockdown technologies induced by lentivirus to upregulate or downregulate TGF-β1 level in mouse HSCs (mHSCs) (mHSCs-TGF-β1 or mHSCs-TGF-βR1sih3). Primary mouse HPCs (mHPCs) were isolated and were cocultured with mHSCs-TGF-β1 and mHSCs-TGF-βR1sih3 for 7 days. Differentiation of mHPCs was detected by quantitative reverse transcriptase polymerase chain reaction analysis and immunofluorence in vitro. mHPCs-E_14.5 cell lines and differently treated mHSCs were cotransplanted into mice spleens immediately after establishment of acute liver injury model for animal studies. Engraftment and differentiation of transplanted cells as well as liver function recovery were measured at the seventh day via different methods. mHSCs-TGF-β1 were transformed into myofibroblasts and highly expressed Jagged1, but that expression was reduced after blockage of TGF-β1 signaling. mHPCs highly expressed downstream markers of Jagged1/Notch signaling and cholangiocyte markers (CK19, SOX9, and Hes1) after coculture with mHSCs-TGF-β1 in vitro. In contrast, mature hepatocyte marker (ALB) was upregulated in mHPCs in coculture conditions with mHSCs-TGF-βR1sih3. At the seventh day of cell transplantation assay, mHPCs-E _14.5 engrafted and differentiated into cholangiocytes after cotransplanting with TGF-β1-knockin mHSCs, but the cells had a tendency to differentiate into hepatocytes when transplanted with TGF-βR1-knockdown mHSCs, which corresponded to in vitro studies. HSCs play an important role in regulating HPCs differentiation into cholangiocytes via the TGF-β1/Jagged1 signaling axis. However, HPCs have a tendency to differentiate into hepatocytes after blockage of TGF-β1 signaling in HSCs.

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Nam A, Han SM, Go DM, Kim DY, Seo KW, Youn HY. Long-Term Management with Adipose Tissue-Derived Mesenchymal Stem Cells and Conventional Treatment in a Dog with Hepatocutaneous Syndrome. J Vet Intern Med 2017;31:1514-1519. [PMID: 28782844 PMCID: PMC5598886 DOI: 10.1111/jvim.14798] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 04/24/2017] [Accepted: 06/29/2017] [Indexed: 12/20/2022] Open

Hsu MJ, Prigent J, Dollet PE, Ravau J, Larbanoix L, Van Simaeys G, Bol A, Grégoire V, Goldman S, Deblandre G, Najimi M, Sokal EM, Lombard CA. Long-Term In Vivo Monitoring of Adult-Derived Human Liver Stem/Progenitor Cells by Bioluminescence Imaging, Positron Emission Tomography, and Contrast-Enhanced Computed Tomography. Stem Cells Dev 2017;26:986-1002. [PMID: 28340549 DOI: 10.1089/scd.2016.0338] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open

Affiliation(s)

Mei-Ju Hsu 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Julie Prigent 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Pierre-Edouard Dollet 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Joachim Ravau 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Lionel Larbanoix 2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium 3 NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, Université de Mons , Mons, Belgium
Gaetan Van Simaeys 2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium 4 Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles , Brussels, Belgium
Anne Bol 5 Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Vincent Grégoire 5 Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Serge Goldman 2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium 4 Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles , Brussels, Belgium
Gisèle Deblandre 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Mustapha Najimi 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium
Etienne M Sokal 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium 6 Cliniques Universitaires Saint-Luc , Brussels, Belgium
Catherine A Lombard 1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium

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Pietrosi G, Chinnici C. Report on Liver Cell Transplantation Using Human Fetal Liver Cells. Methods Mol Biol 2017;1506:283-294. [PMID: 27830561 DOI: 10.1007/978-1-4939-6506-9_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]

Herrero A, Prigent J, Lombard C, Rosseels V, Daujat-Chavanieu M, Breckpot K, Najimi M, Deblandre G, Sokal EM. Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy. Cell Transplant 2016;26:351-364. [PMID: 27657746 DOI: 10.3727/096368916x692960] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open

Mandal A, Raju S, Viswanathan C. Cryopreserved hepatic progenitor cells derived from human embryonic stem cells can arrest progression of liver fibrosis in rats. Cell Biol Int 2016;40:1107-15. [PMID: 27453189 DOI: 10.1002/cbin.10649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 07/22/2016] [Indexed: 11/06/2022]

Merlin S, Bhargava KK, Ranaldo G, Zanolini D, Palestro CJ, Santambrogio L, Prat M, Follenzi A, Gupta S. Kupffer Cell Transplantation in Mice for Elucidating Monocyte/Macrophage Biology and for Potential in Cell or Gene Therapy. THE AMERICAN JOURNAL OF PATHOLOGY 2016;186:539-51. [PMID: 26773351 DOI: 10.1016/j.ajpath.2015.11.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 10/16/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023]

Pietrosi G, Vizzini G, Gerlach J, Chinnici C, Luca A, Amico G, D'amato M, Conaldi PG, Petri SL, Spada M, Tuzzolino F, Alio L, Schmelzer E, Gridelli B. Phases I-II Matched Case-Control Study of Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Disease. Cell Transplant 2015;24:1627-38. [DOI: 10.3727/096368914x682422] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open

Abstract Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with endstage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 ( p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group ( p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study. Collapse

Affiliation(s)

Giada Pietrosi Hepatology Unit, Department of Medicine, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Giovanni Vizzini Hepatology Unit, Department of Medicine, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Jorg Gerlach McGowan Institute for Regenerative Medicine, Departments of Surgery and Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Cinzia Chinnici Fondazione Ri.MED, Palermo, Italy
Angelo Luca Department of Diagnostic and Therapeutics Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Giandomenico Amico Fondazione Ri.MED, Palermo, Italy
Monica D'amato Fondazione Ri.MED, Palermo, Italy
Pier Giulio Conaldi Department of Laboratory Medicine and Advanced Biotechnologies, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Sergio Li Petri Abdominal and Transplantation Surgery Unit, Department of Surgery, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Marco Spada Abdominal and Transplantation Surgery Unit, Department of Surgery, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Fabio Tuzzolino Research Office, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy
Luigi Alio Department of Obstetrics and Gynecology, Civico Hospital, Palermo, Italy
Eva Schmelzer McGowan Institute for Regenerative Medicine, Departments of Surgery and Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Bruno Gridelli Abdominal and Transplantation Surgery Unit, Department of Surgery, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo, Italy

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Habeeb MA, Vishwakarma SK, Bardia A, Khan AA. Hepatic stem cells: A viable approach for the treatment of liver cirrhosis. World J Stem Cells 2015;7:859-865. [PMID: 26131316 PMCID: PMC4478632 DOI: 10.4252/wjsc.v7.i5.859] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 02/14/2015] [Accepted: 04/16/2015] [Indexed: 02/06/2023] Open

Abstract

Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation.

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Hickey RD, Mao SA, Amiot B, Suksanpaisan L, Miller A, Nace R, Glorioso J, Peng KW, Ikeda Y, Russell SJ, Nyberg SL. Noninvasive 3-dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene. Liver Transpl 2015;21:442-53. [PMID: 25482651 PMCID: PMC5957080 DOI: 10.1002/lt.24057] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Accepted: 11/30/2014] [Indexed: 12/24/2022]

Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol 2015;62:S157-69. [PMID: 25920085 DOI: 10.1016/j.jhep.2015.02.040] [Citation(s) in RCA: 218] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 02/20/2015] [Accepted: 02/27/2015] [Indexed: 02/08/2023]

Dollé L, Theise ND, Schmelzer E, Boulter L, Gires O, van Grunsven LA. EpCAM and the biology of hepatic stem/progenitor cells. Am J Physiol Gastrointest Liver Physiol 2015;308:G233-50. [PMID: 25477371 PMCID: PMC4329473 DOI: 10.1152/ajpgi.00069.2014] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Shim G, Lee S, Han J, Kim G, Jin H, Miao W, Yi TG, Cho YK, Song SU, Oh YK. Pharmacokinetics and in vivo fate of intra-articularly transplanted human bone marrow-derived clonal mesenchymal stem cells. Stem Cells Dev 2015;24:1124-32. [PMID: 25519508 DOI: 10.1089/scd.2014.0240] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open

Spriet M, Hunt GB, Walker NJ, Borjesson DL. SCINTIGRAPHIC TRACKING OF MESENCHYMAL STEM CELLS AFTER PORTAL, SYSTEMIC INTRAVENOUS AND SPLENIC ADMINISTRATION IN HEALTHY BEAGLE DOGS. Vet Radiol Ultrasound 2015;56:327-34. [DOI: 10.1111/vru.12243] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 10/05/2014] [Indexed: 12/29/2022] Open

Defresne F, Tondreau T, Stéphenne X, Smets F, Bourgois A, Najimi M, Jamar F, Sokal EM. Biodistribution of adult derived human liver stem cells following intraportal infusion in a 17-year-old patient with glycogenosis type 1A. Nucl Med Biol 2014;41:371-5. [PMID: 24607438 DOI: 10.1016/j.nucmedbio.2014.01.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 01/10/2014] [Accepted: 01/13/2014] [Indexed: 01/04/2023]

Consideration of bone regeneration effect of stem cells: comparison between adipose-derived stem cells and demineralized bone matrix. J Craniofac Surg 2014;25:189-95. [PMID: 24406576 DOI: 10.1097/scs.0000000000000377] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open

Abstract

BACKGROUND

Currently, many studies have sought to address the regeneration of extensive bone defects using stem cells. Here, the authors injected adipose-derived stem cells and demineralized bone matrix (DBM) into areas of bone defect in rabbits and compared their effect on bone regeneration to study the clinical usefulness of stem cells.

METHODS

This study used 20 male New Zealand white rabbits. Four craniectomies were made in 20 male New Zealand white rabbits' calvaria, and 4 different groups of experimental conditions were applied to each of the 4 cranial defects. To the first group, 0.2 mL of DBX, a commercially available clinical preparation ofDBM, was applied with fibrin glue. To the second group, 0.2 mL of adipose-derived stem cells, with confirmed bone differentiation ability, was applied with fibrin glue. To the third group, 0.1 mL of DBX, 0.1 mL of adipose-derived stem cells, and fibrin glue were applied. The fourth group of defects acted as the control and was left unaltered. After 6 weeks, regenerated bone from each defect site in each rabbit was collected and measured for volume change. Bone regeneration was assessed with three-dimensional skull bone computed tomography and histological analysis.

RESULTS

Osteoblasts were confirmed in all defect groups after 6 weeks. Overall, bone regeneration was weakest in the control group, whereas other groups of defects showed distinct bone regeneration. In particular, group 3, to which adipose-derived stem cells and DBM were applied, demonstrated the most active regeneration.

CONCLUSIONS

Both adipose-derived stem cells and DBM demonstrated regeneration effect on cranial defects in rabbits, but it is difficult to conclude which was better, because in each case the amount of regenerated bone was within the margin of error. However, as the most active bone regeneration was observed when both adipose-derived stem cells and DBM were applied together, this combination could be helpful in the correction of extensive bone defects.

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Liu WH, Ren LN, Chen T, You N, Liu LY, Wang T, Yan HT, Luo H, Tang LJ. Unbalanced distribution of materials: the art of giving rise to hepatocytes from liver stem/progenitor cells. J Cell Mol Med 2014;18:1-14. [PMID: 24286303 PMCID: PMC3916112 DOI: 10.1111/jcmm.12183] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 10/08/2013] [Indexed: 12/12/2022] Open

Shin S, Kaestner KH. The origin, biology, and therapeutic potential of facultative adult hepatic progenitor cells. Curr Top Dev Biol 2014;107:269-92. [PMID: 24439810 DOI: 10.1016/b978-0-12-416022-4.00010-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]

Trela JM, Spriet M, Padgett KA, Galuppo LD, Vaughan B, Vidal MA. Scintigraphic comparison of intra-arterial injection and distal intravenous regional limb perfusion for administration of mesenchymal stem cells to the equine foot. Equine Vet J 2013;46:479-83. [PMID: 23834199 DOI: 10.1111/evj.12137] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 06/29/2013] [Indexed: 12/26/2022]

Abstract

REASONS FOR PERFORMING STUDY

Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use.

OBJECTIVES

Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v. RLP through the lateral palmar digital vein.

STUDY DESIGN

In vivo experimental study.

METHODS

(99m) Tc-HMPAO-labelled MSCs were injected through the median artery of one limb and the lateral palmar digital vein of the other limb of 6 horses under general anaesthesia. No tourniquet was used for the i.a. injection. A pneumatic tourniquet was placed on the metacarpus for i.v. injection. Scintigraphic images were obtained up to 24 h after injection.

RESULTS

Intra-arterial injection resulted in MSCs retention within the limb despite the absence of a tourniquet and no thrombosis was observed. Both i.a. injection and i.v. RLP led to distribution of MSCs to the foot. The i.a. injection resulted in a more homogeneous distribution. The MSC uptake was higher with i.v. RLP at the initial timepoints, but no significant difference was present at 24 h.

CONCLUSIONS

Both i.a. injection through the median artery without a tourniquet and i.v. RLP performed through the lateral palmar digital vein under general anaesthesia are safe and reliable methods for administration of MSCs to the equine foot. The i.a. technique is preferred owing to the better distribution, but is technically more challenging. The feasibility of performing these techniques on standing horses remains to be investigated.

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Lombard CA, Prigent J, Sokal EM. Human Liver Progenitor Cells for Liver Repair. CELL MEDICINE 2013;5:1-16. [PMID: 26858860 PMCID: PMC4733913 DOI: 10.3727/215517913x666459] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Boeykens N, Ponsaerts P, Van der Linden A, Berneman Z, Ysebaert D, De Greef K. Injury-dependent retention of intraportally administered mesenchymal stromal cells following partial hepatectomy of steatotic liver does not lead to improved liver recovery. PLoS One 2013;8:e69092. [PMID: 23874878 PMCID: PMC3715456 DOI: 10.1371/journal.pone.0069092] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 06/04/2013] [Indexed: 12/21/2022] Open

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury. Exp Cell Res 2013;319:2266-74. [PMID: 23806280 DOI: 10.1016/j.yexcr.2013.06.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Revised: 06/13/2013] [Accepted: 06/15/2013] [Indexed: 01/05/2023]

Hepatocyte labeling with ⁹⁹mTc-GSA: a potential non-invasive technique for tracking cell transplantation. Int J Artif Organs 2013;35:450-7. [PMID: 22476879 DOI: 10.5301/ijao.5000096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2012] [Indexed: 11/20/2022]

Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms. Exp Mol Pathol 2013;94:466-73. [PMID: 23534987 DOI: 10.1016/j.yexmp.2013.03.002] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2012] [Accepted: 03/07/2013] [Indexed: 12/15/2022]

Wimpenny I, Markides H, El Haj AJ. Orthopaedic applications of nanoparticle-based stem cell therapies. Stem Cell Res Ther 2012;3:13. [PMID: 22520594 PMCID: PMC3392773 DOI: 10.1186/scrt104] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open

Abstract

Stem cells have tremendous applications in the field of regenerative medicine and tissue engineering. These are pioneering fields that aim to create new treatments for disease that currently have limited therapies or cures. A particularly popular avenue of research has been the regeneration of bone and cartilage to combat various orthopaedic diseases. Magnetic nanoparticles (MNPs) have been applied to aid the development and translation of these therapies from research to the clinic. This review highlights contemporary research for the applications of iron-oxide-based MNPs for the therapeutic implementation of stem cells in orthopaedics. These MNPs comprise of an iron oxide core, coated with a choice of biological polymers that can facilitate the uptake of MNPs by cells through improving endocytic activity. The combined use of these oxides and the biological polymer coatings meet biological requirements, effectively encouraging the use of MNPs in regenerative medicine. The association of MNPs with stem cells can be achieved via the process of endocytosis resulting in the internalisation of these particles or the attachment to cell surface receptors. This allows for the investigation of migratory patterns through various tracking studies, the targeting of particle-labelled cells to desired locations via the application of an external magnetic field and, finally, for activation stem cells to initiate various cellular responses to induce the differentiation. Characterisation of cell localisation and associated tissue regeneration can therefore be enhanced, particularly for in vivo applications. MNPs have been shown to have the potential to stimulate differentiation of stem cells for orthopaedic applications, without limiting proliferation. However, careful consideration of the use of active agents associated with the MNP is suggested, for differentiation towards specific lineages. This review aims to broaden the knowledge of current applications, paving the way to translate the in vitro and in vivo work into further orthopaedic clinical studies.

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Puppi J, Strom SC, Hughes RD, Bansal S, Castell JV, Dagher I, Ellis ECS, Nowak G, Ericzon BG, Fox IJ, Gómez-Lechón MJ, Guha C, Gupta S, Mitry RR, Ohashi K, Ott M, Reid LM, Roy-Chowdhury J, Sokal E, Weber A, Dhawan A. Improving the techniques for human hepatocyte transplantation: report from a consensus meeting in London. Cell Transplant 2012;21:1-10. [PMID: 21457616 DOI: 10.3727/096368911x566208] [Citation(s) in RCA: 151] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open

Abstract

On September 6 and 7, 2009 a meeting was held in London to identify and discuss what are perceived to be current roadblocks to effective hepatocyte transplantation as it is currently practiced in the clinics and, where possible, to offer suggestions to overcome the blocks and improve the outcomes for this cellular therapy. Present were representatives of most of the active clinical hepatocyte transplant programs along with other scientists who have contributed substantial basic research to this field. Over the 2-day sessions based on the experience of the participants, numerous roadblocks or challenges were identified, including the source of cells for the transplants and problems with tracking cells following transplantation. Much of the discussion was focused on methods to improve engraftment and proliferation of donor cells posttransplantation. The group concluded that, for now, parenchymal hepatocytes isolated from donor livers remain the best cell source for transplantation. It was reported that investigations with other cell sources, including stem cells, were at the preclinical and early clinical stages. Numerous methods to modulate the immune reaction and vascular changes that accompany hepatocyte transplantation were proposed. It was agreed that, to obtain sufficient levels of repopulation of liver with donor cells in patients with metabolic liver disease, some form of liver preconditioning would likely be required to enhance the engraftment and/or proliferation of donor cells. It was reported that clinical protocols for preconditioning by hepatic irradiation, portal vein embolization, and surgical resection had been developed and that clinical studies using these protocols would be initiated in the near future. Participants concluded that sharing information between the groups, including standard information concerning the quality and function of the transplanted cells prior to transplantation, clinical information on outcomes, and standard preconditioning protocols, would help move the field forward and was encouraged.

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Human hepatocyte transplantation: current experience and future challenges. Nat Rev Gastroenterol Hepatol 2010;7:288-98. [PMID: 20368738 DOI: 10.1038/nrgastro.2010.44] [Citation(s) in RCA: 257] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Habeeb MA, Srinivas G, Raj TA, Tiwari SK, Kumaresan K, Venkateswarlu J, Pande G, Habibullah CM. Human Fetal Liver-Derived Stem Cell Transplantation as Supportive Modality in the Management of End-Stage Decompensated Liver Cirrhosis. Cell Transplant 2010. [DOI: 10.3727/096368909x484707a] [Citation(s) in RCA: 115] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open