Abstract
BackgroundClinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL).MethodsIn this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors.ResultsWe characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells.ConclusionsOur study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria.Clinical trialsUse of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007. Registered August 26, 2013.MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540. Registered April 23, 2013.Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027. Registered October 31, 2014.Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145. Registered August 17, 2006.A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283. Registered May 18, 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0370-8) contains supplementary material, which is available to authorized users.
Highlights
Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of Mesenchymal stromal cell (MSC) may impact therapeutic outcomes
The release criteria used to characterize Adipose derived mesenchymal stromal cell (AMSC) utilized are shown in Fig. 1a, where AMSCs must express classical markers including CD44, CD73, CD90, CD105, and HLA-ABC, and lack the expression of HLA-DR, CD14, and CD45 [11]
The data presented here support the literature demonstrating that these markers are characteristic of AMSCs and are present on clinical-grade AMSCs expanded in human platelet lysate (hPL)
Summary
Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Adipose tissue has been identified as an MSC-rich tissue, in which 1–10 % of the stromal fraction is MSCs [9, 10], which undergo multi-lineage differentiation in vitro [9,10,11,12,13]. These attributes are advantageous and permit autologous transplantation, which is important for non-fatal diseases (e.g., wound healing, osteoarthritis, or aesthetic procedures). The anatomical location of harvesting may have some impact on the yield of adipose-derived MSCs (AMSCs) [14, 15], variability in processing, manufacturing, and delivery of MSC/AMSCs may have larger implications on cell therapy outcomes [16]
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