Biological functions of mesenchymal stem cells and clinical implications

Abstract

Mesenchymal stem cells (MSCs) are isolated from multiple biological tissues-adult bone marrow and adipose tissues and neonatal tissues such as umbilical cord and placenta. In vitro, MSCs show biological features of extensive proliferation ability and multipotency. Moreover, MSCs have trophic, homing/migration and immunosuppression functions that have been demonstrated both in vitro and in vivo. A number of clinical trials are using MSCs for therapeutic interventions in severe degenerative and/or inflammatory diseases, including Crohn's disease and graft-versus-host disease, alone or in combination with other drugs. MSCs are promising for therapeutic applications given the ease in obtaining them, their genetic stability, their poor immunogenicity and their curative properties for tissue repair and immunomodulation. The success of MSC therapy in degenerative and/or inflammatory diseases might depend on the robustness of the biological functions of MSCs, which should be linked to their therapeutic potency. Here, we outline the fundamental and advanced concepts of MSC biological features and underline the biological functions of MSCs in their basic and translational aspects in therapy for degenerative and/or inflammatory diseases.

Keywords: Cell functions; Cell identity; Cell therapy; Mesenchymal stem/stromal cells.

Fig. 1

Medical conditions targeted by MSC therapy. Diagram of the conditions targeted by MSCs by proportion of trials. Data were obtained using a recurrent search of keywords for medical conditions (appearing in the diagram) associated with mesenchymal stem/stromal cells at ClinicalTrials.gov. The search was completed on April 2019. The group “medical conditions for degenerative disorders” represents about 18% of total trials, and inflammatory disorders combined (autoimmune diseases, transplant immune rejection, severe inflammatory diseases) represent about 45% of all trials and most of the clinical trials of MSCs for treatment

Fig. 2

Worldwide usage and progress of MSC therapy. Proportion of clinical trials of MSCs by location. Data were obtained by a search of ClinicalTrials.gov completed on June 2018. a East Asia (mostly China) followed by Europe and North America (mostly United States) are the locations of 70% of all clinical trials investigating MSCs as treatment. b Phase 1 and 2 clinical trials of MSCs as treatment represent about 85% of the total number, whereas more advanced clinical trials in phases 3 and 4 represent less than 10%. c Increased proportion of pharmaceutical industry-sponsored clinical trials investigating MSCs as treatment progressing to the advanced phase. Academia-sponsored clinical trials represent most of the clinical trials of MSCs as treatment, about 60% at least. d Sources of MSCs by proportion of clinical trials. Data were obtained using a recurrent search of keywords for sources of MSCs in trials (appearing in the diagram) at ClinicalTrials.gov. The search was completed on June 2018. Bone marrow-derived MSCs (BM-MSCs) are investigated in about 40% of total trials, followed by umbilical cord-derived MSCs (UC-MSCs) at 20% and adipose tissue-derived MSCs (ASCs) at 10%

Fig. 3

Biological functions of MSCs. The five biological functions of MSCs with interest in therapeutics: (1) proliferation function, (2) multipotency function, (3) homing/migration function, (4) trophic function, and (5) immunosuppression function. The diagram gives three representative molecules involved in each of these functions. HIF-1 hypoxia-inducible factor 1, Wnt wingless type, PPAR-γ2 peroxisome proliferator-activated receptor 2, SOX9 sex-determining region of the Y chromosome-box 9, RUNX-2 runt-related transcription factor 2, Adipo adipocyte, Chondro chondroblast, Osteo osteoblast, BDNF brain-derived neurotrophic factor, HGF hepatocytes growth factor, VEGF vascular endothelial growth factor, IL interleukin, IDO indoleamine 2,3 dioxygenase, PGE2 prostaglandin E2, CD cluster of differentiation, CXCR CXC chemokine receptor, VCAM-1 vascular cell adhesion molecular 1