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Review
, 6 (12), 2173-2185

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

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Review

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Rebekah M Samsonraj et al. Stem Cells Transl Med.

Abstract

Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185.

Keywords: Bone marrow; Characterization; Mesenchymal stem/stromal cells; Regenerative medicine; Release criteria.

Figures

Figure 1
Figure 1
Profiling of MSCs. The diagram depicts the key parameters for the characterization of adult stem cells from different sources. Three of these parameters are linked to cell growth, survival, quiescence and/or senescence (i.e., viability and growth, CFU‐Fs, telomere length), two are associated with cell identity (i.e., multilineage differentiation and surface marker expression), and the remaining two refer to the ability of MSCs to communicate with their microenvironment (i.e., immunomodulation and paracrine effects of trophic factors). Immunomodulation is important for regulating macrophage function during tissue repair (e.g., M1 to M2 macrophage transition) and for anticipating graft rejection (e.g., mixed lymphocyte reaction). Collectively, these parameters should be considered for the development of release criteria that validate the quality of GMP‐grade MSCs for stem cell therapy. Abbreviations: MSCs, mesenchymal stem cells; CFU‐Fs, colony‐forming units‐fibroblastic.
Figure 2
Figure 2
Dual functions of MSCs in tissue regeneration and repair. MSCs play a central role during regeneration and repair of musculoskeletal tissues (i.e., bone, cartilage, ligament, tendon, muscle and synovium). In addition, MSCs provide a microenvironment for hematopoietic stem cells, including cells of the myeloid and lymphoid lineages. Effects of MSCs on their microenvironment are mediated by secretion of trophic factors that have both autocrine and paracrine functions. Abbreviation: MSCs, mesenchymal stem cells.
Figure 3
Figure 3
Interactions of MSC with immune cells. MSCs secrete soluble molecules, such as nitric oxide, PGE2, IDO, IL‐10 and TGFβ1. The secretion of these factors suppresses the proliferation and/or activity of a variety of immune cells, including T cells, B cells, Natural Killer cells, and dendritic cells, as well as activated Tregs. Abbreviations: IDO, indoleamine 2, 3‐dioxygenase; IL‐10, interleukin‐10; MSCs, mesenchymal stem cells; PGE2, prostaglandin; TGFβ1, transforming growth factor‐beta 1; Tregs, regulatory T cells.
Figure 4
Figure 4
Standard operating procedures for isolating mesenchymal stem cells (MSCs). The diagram shows the basic steps for isolating and validating MSCs from bone marrow aspirates derived from either human donors or patients, including evaluation of key potency parameters of these cells before release to the clinic. Abbreviations: BM, bone marrow; cPD, cumulative population doubling; HSC, hematopoietic stem cells; ISCT, International Society for Cellular Therapy; MNC, mononuclear cells; PD, population doubling; PDGFR‐α, platelet‐derived growth factor receptor‐alpha; STRO‐1, stromal antigen‐1. Asterisk (*) indicates proposition of additional criteria that could potentially facilitate better selection of MSCs.
Figure 5
Figure 5
Mesenchymal stem cells (MSCs) in clinical trials and stem cell market forecast. (A): MSC‐based clinical trials were charted by region based on search results sourced from https://ClinicalTrials.gov (retrieved July 1, 2017). (B): Scopus search results show the number of stem cell research articles published between 1995 and 2015, indicating the rising number of published studies on MSCs (retrieved July 1, 2017; https//:www.scopus.com).

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