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Purita J, Lana JFSD, Kolber M, Rodrigues BL, Mosaner T, Santos GS, Caliari-Oliveira C, Huber SC. Bone marrow-derived products: A classification proposal - bone marrow aspirate, bone marrow aspirate concentrate or hybrid? World J Stem Cells 2020; 12:241-250. [PMID: 32399133 PMCID: PMC7202927 DOI: 10.4252/wjsc.v12.i4.241] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 02/07/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Degenerative musculoskeletal disorders are one of the top causes of pain and disability in the adult population. Current available alternatives to mitigate symptoms include conservative treatments such as the administration of pharmacological agents and an educative approach towards lifestyle modification. The use of certain analgesics, such as opiates and corticosteroids, delivers short term results but do not address the etiological source of pain and disability. Also, prolonged use of such medications may cause additional complications. Therefore, the demand for musculoskeletal tissue regeneration has led to an alternative approach referred to as "orthobiologics". This alternative is based on cellular and molecular components capable of inducing and promoting tissue repair. Bone marrow (BM) aspirate (BMA) and concentrate are well-known orthobiologics used to treat musculoskeletal conditions. Orthobiologics derived from the BM have been discussed in the literature; however, the lack of standardization regarding collection and processing protocols presents a challenge for generalization of study outcomes and determination of efficacy. Since BM-derived orthobiologics have not yet been classified, to our knowledge, this manuscript proposes the ACH classification system, which speaks to BMA (A), BMA and concentrate (C) and hybrid (H), which combines A and C. This classification proposes and describes 8 parameters that are relevant for the quality of biological products. The more parameters used would imply greater characterization and complexity of the evaluation of the biological product used. The ACH classification envisages a necessary contribution to the comprehension of both clinical procedures and research outcomes, ultimately ushering in a standardization of best practice.
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Affiliation(s)
- Joseph Purita
- Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
| | | | - Morey Kolber
- Department of Physical Therapy, Nova Southeastern University, Fort Lauderdale, FL 33314, United States
| | | | - Tomas Mosaner
- Institute of Bone and Cartilage, Indaiatuba, SP 13334-170, Brazil
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Meyer J, Salamon A, Herzmann N, Adam S, Kleine HD, Matthiesen I, Ueberreiter K, Peters K. Isolation and differentiation potential of human mesenchymal stem cells from adipose tissue harvested by water jet-assisted liposuction. Aesthet Surg J 2015; 35:1030-9. [PMID: 26006726 DOI: 10.1093/asj/sjv075] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2015] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND In recent years the therapeutic application of extracted adipose tissue for autologous fat grafting and the application of adipose tissue-derived mesenchymal stem cells (adMSC) isolated thereof has progressed. Water-jet assisted liposuction (WAL) is 1 procedure for harvesting adipose tissue and provides a favorable aesthetic outcome combined with high tissue protection. Tissue aspirated by WAL has been successfully applied in grafting procedures. OBJECTIVES The aims of this study were to confirm the tissue viability and to understand the abundance and mesenchymal differentiation capacity of stem cells within the tissue. METHODS We analyzed tissue integrity of WAL tissue particles via fluorescence microscopy. The adMSC content was determined by isolating the cells from the tissue. The mesenchymal differentiation capacity was confirmed with cytochemical staining methods. RESULTS The stromal vascular fraction of WAL tissue showed high viability and contained an average of 2.6 × 105 CD34-positive cells per milliliter of tissue. Thus WAL tissue contains a high number of stem cells. Furthermore adMSC isolated from WAL tissue showed typical mesenchymal differentiation potential. CONCLUSIONS WAL of adipose tissue is well suited for autologous fat grafting because it retains tissue viability. Furthermore it is a valid source for the subsequent isolation of adMSC with multipotent differentiation potential. LEVEL OF EVIDENCE 3 Therapeutic.
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Affiliation(s)
- Juliane Meyer
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Achim Salamon
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Nicole Herzmann
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Stefanie Adam
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Hans-Dieter Kleine
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Inge Matthiesen
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Klaus Ueberreiter
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
| | - Kirsten Peters
- Mrs Meyer and Mrs Herzmann are PhD Students, Dr Salamon is a Post-doctoral Fellow, Mrs Adam is a Technical Assistant, and Dr Peters is Head of the Stem Cell Biology Group, Department of Cell Biology, Rostock University Medical Center, Rostock, Germany. Dr Kleine is on the Executive Board of Seracell Stammzelltechnologie GmbH, Rostock, Germany. Dr Matthiesen is Head of the Department of Medical Affairs, human med AG, Schwerin, Germany. Dr Ueberreiter is a Plastic Surgeon in private practice in Birkenwerder, Germany
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Donor stromal cells from human blood engraft in NOD/SCID mice. Blood 2000. [DOI: 10.1182/blood.v96.12.3971.h8003971_3971_3978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Little is known about the presence, frequency, and in vivo proliferative potential of stromal cells within blood-derived hematopoietic transplants. In this study, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were injected with human CD34+ peripheral blood cells (PBCs) or cord blood cells (CBCs, either enriched for CD34 or density-gradient separated mononuclear cells). Flow cytometric analysis 5 to 11 weeks after transplantation revealed the presence of a human lymphomyeloid hematopoiesis within the murine bone marrow. Immunohistochemical staining of bone marrow cell suspensions using human-specific antibodies showed human cells staining positive for human fibroblast markers, human von Willebrand factor (vWF) and human KDR (vascular endothelial growth factor receptor-2) in mice transplanted with CD34+ PBCs or CBCs, with mean frequencies between 0.6% and 2.4%. In stromal layers of bone marrow cultures established from the mice, immunohistochemical staining using human-specific antibodies revealed flattened reticular cells or spindle-shaped cells staining positive with human-specific antifibroblast antibodies (mean frequency, 2.2%). Cell populations of more rounded cells stained positive with human-specific antibodies recognizing CD34 (1.5%), vWF (2.2%), and KDR (1.6%). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and subsequent complementary DNA sequencing detected transcripts of human KDR (endothelial specific) and human proline hydroxylase-α (fibroblast specific) within the bone marrow and spleen of transplanted mice. Analysis of nontransplanted control mice yielded negative results in immunocytochemistry and RT-PCR. Cells expressing endothelial and fibroblast markers were also detected in the grafts before transplantation, and their numbers increased up to 3 log in vivo after transplantation. These results indicate that stromal progenitor cells are present in human cytokine-mobilized peripheral blood or cord blood that engraft in NOD/SCID mice.
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Kashiwakura I, Kuwabara M, Inanami O, Murakami M, Hayase Y, Takahashi TA, Takagi Y. Radiation sensitivity of megakaryocyte colony-forming cells in human placental and umbilical cord blood. Radiat Res 2000; 153:144-52. [PMID: 10629613 DOI: 10.1667/0033-7587(2000)153[0144:rsomcf]2.0.co;2] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The in vitro radiation sensitivity of CFU-Meg isolated from human placental and umbilical cord blood was evaluated in plasma clot cultures stimulated by recombinant human cytokines, including thrombopoietin, the FLT3 ligand (FLT3LG), interleukin-3, interleukin-11 and stem cell factor. The CD34(+) cells were irradiated with X rays at a dose rate of 73 cGy/ min. The megakaryocyte colonies were identified by using an FITC-conjugated antibody to glycoprotein IIbIIIa and were classified into two groups based on colony size: large colonies (immature CFU-Meg) and small colonies (mature CFU-Meg). Treatment with thrombopoietin alone or in combination with FLT3LG and/or interleukin-11 gave exponential radiation survival curves (D(0) for immature CFU-Meg = 56-77 cGy, D(0) for mature CFU-Meg = 86 cGy-1.12 Gy), while marked shoulders were observed on the survival curves for colonies supported by the combination of thrombopoietin, interleukin-3 and stem cell factor (D(0) for immature CFU-Meg = 89- 98 cGy; D(0) for mature CFU-Meg = 1. 25-1.31 Gy). Our results showed that the immature CFU-Meg were more radiosensitive than the mature CFU-Meg and that the combination of cytokines, including thrombopoietin, interleukin-3 and stem cell factor, affected the radiation sensitivity of CFU-Meg to the same extent as with thrombopoietin alone or in combination with FLT3LG and/or interleukin-11.
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Affiliation(s)
- I Kashiwakura
- Laboratory of Radiopharmaceutical Sciences, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru 047-0264, Japan
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