Abstract
Mesenchymal stroma cells (MSCs) have a high potential for novel cell therapy approaches in clinical transplantation. Commonly used bone marrow-derived MSCs (BM-MSCs), however, have a restricted proliferative capacity and cultures are difficult to standardize. Recently developed human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) might represent an alternative and unlimited source of hMSCs. We therefore compared human ES-cell-derived MSCs (hES-MP002.5 cells) to normal human bone marrow-derived MSCs (BM-MSCs). hES-MP002.5 cells had lower yet reasonable CFU-F capacity compared with BM-MSC (8±3 versus 29±13 CFU-F per 100 cells). Both cell types showed similar immunophenotypic properties, i.e. cells were positive for CD105, CD73, CD166, HLA-ABC, CD44, CD146, CD90, and negative for CD45, CD34, CD14, CD31, CD117, CD19, CD 271, SSEA-4 and HLA-DR. hES-MP002.5 cells, like BM-MSCs, could be differentiated into adipocytes, osteoblasts and chondrocytes in vitro. Neither hES-MP002.5 cells nor BM-MSCs homed to the bone marrow of immune-deficient NSG mice following intravenous transplantation, whereas intra-femoral transplantation into NSG mice resulted in engraftment for both cell types. In vitro long-term culture-initiating cell assays and in vivo co-transplantation experiments with cord blood CD34+ hematopoietic cells demonstrated furthermore that hES-MP002.5 cells, like BM-MSCs, possess potent stroma support function. In contrast to BM-MSCs, however, hES-MP002.5 cells showed no or only little activity in mixed lymphocyte cultures and phytohemagglutinin (PHA) lymphocyte stimulation assays. In summary, ES-cell derived MSCs might be an attractive unlimited source for stroma transplantation approaches without suppressing immune function.
Highlights
Cultured mesenchymal stromal cells (MSCs) have gained considerable interest as potential candidates for cell therapy
Results human embryonic stem (hES)-MP002.5 generated Colony-forming unit fibroblast (CFU-F) in-vitro Single cell suspensions were prepared from hES-MP002.5 cells and bone marrow-derived MSCs (BM-MSCs) and tested for their mesenchymal progenitor growth using the standard CFU-F assay
Bone marrow MSCs – as other MSC preparations derived from single donor adult stroma stem cell sources – are primary cells, which have certain properties that limit a broader clinical application in larger cohorts of patients
Summary
Cultured mesenchymal stromal cells (MSCs) have gained considerable interest as potential candidates for cell therapy. MSCs have a number of remarkable properties, such as high proliferation and differentiation potential, a broad cytokine production capacity and – best demonstrated for bone marrow MSCs – immune modulatory effects [1,2]. MSCs are culture-derived from a small population of stromal stem cells, which are present at low frequency in adult connective tissues [9,10]. MSCs for clinical use have far been derived mostly from adult bone marrow, yet there are several alternative sources such as fat tissue, cord blood and umbilical cord, amniotic membrane and other tissues [11]. Harvesting MSCs from adult tissues requires the availability of a suitable donor, and in some cases – such as bone marrow – invasive procedures need to be performed for cell harvest with potential side effects for the donors. Cultured-derived MSCs are heterogeneous and difficult to standardize [14,15]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have