Mesenchymal Stromal Cell Characteristics Vary Depending on Their Origin

Abstract

Mesenchymal stromal cells (MSCs) are rare progenitor cells that can be isolated from various tissues. They exhibit multilineage differentiation potential, support regenerative processes, and interact with various immune cells. Therefore, MSCs represent a promising tool for regenerative medicine. However, source-dependent and donor-dependent differences of MSC properties, including implications on their clinical application are still largely unknown. We evaluated MSCs derived from perinatal tissues umbilical cord (UC) and amniotic membrane (AM) in comparison to adult MSCs from bone marrow (BM), which were used as gold standard. We found genetic background-independent differences between MSCs from UC and AM. While AM-and UC-MSCs were closer to each other than to BM-MSCs, they also exhibited differences between each other. AM-MSCs from different donors but not UC-MSCs displayed high interdonor variability. In addition, we show that although all MSCs expressed similar surface markers, MSC populations from UC and AM showed differential profiles of gene expression and paracrine factor secretion to BM-derived MSCs. Notably, pathway analysis of gene expression data revealed intriguing differences between MSCs suggesting that MSCs from UC and AM possess in general a higher potential of immunomodulatory capacity, whereas BM-MSCs showed a higher potential of supporting regenerative processes as exemplified by neuronal differentiation and development. These differences between perinatal and BM-derived MSCs may be relevant for clinical applications.

Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey

“…In addition, the allosuppressive potential of six freeze-thawed MEP (as usually administered to patients) demonstrated a consistent allosuppressive effect in vitro (Figure 2B), indicating the equipotency of MSC batches (mean 52±8.7%). [4]. FISH analysis using a 2-color probe for chromosome 5p15 (hTERT) and 5q35 (NSD1) and a 3-color break-apart probe for the MYC gene at chromosomal locus 8q24 demonstrated that the majority of MEP possessed a normal diploid pattern ( Figure 3B and C).…”

“…Despite the general consensus that MSCs appear to be welltolerated, safe and effective for the treatment of various diseases, there has been limited progress in this field due to inconsistencies in the outcome of clinical trials. These inconsistencies may be attributed to the lack of a standardized methodology for MSC generation 2 and MSC dosing, the heterogeneity in MSC potency between donors 3 and tissue sources, 4 and the variable number of MSC progenitor cells between tissue samples. 5 MSCs exhibit donor-specific variations in their immunosuppressive properties not only at the donor level, 3,6 but also at the clonal level.…”

Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue

“…Firstly, while mesodermal differentiation capacity is a defining characteristic of MSC, it is likely of secondary importance [23][24][25] , especially where the therapeutic benefit is likely to be derived from the MSC paracrine secretions 26 . Secondly, although Dominici et al proposed minimal criteria for the clinical production of human adult bone marrow-derived MSC 16 , more recent studies indicate MSC from different niches have different inherent properties and differentiation capabilities 5,13,[27][28][29][30][31][32] . In fact, Parolini et al proposed that placenta-derived MSC should differentiate into "one or more mesodermal" lineages rather than all three lineages 10 .…”

Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells

“…MSCs were raised from the aortagonad-mesonephros (AGM), 17 placental tissue, umbilical cord artery and vein as well as from bone marrow (BM) fat and mononuclear cells (MNCs). Like bona fide MSCs, 18,19 all obtained stromal cells expressed the cell surface antigens CD44, CD73, CD90, CD105 and CD146, were negative for CD14, CD31, CD34 and CD45 ( Fig. 2A, Fig.…”