Abstract

Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time‐consuming tissue dissection. MSC can be obtained easily via briefly digesting complete segments of the umbilical cord, likely containing heterogenous or mixed populations of MSC (MC‐MSC). MC‐MSC are generally less well characterized than WJ‐MSC, but nevertheless represent a potentially valuable population of MSC. This study aimed to further characterize MC‐MSC in comparison to WJ‐MSC and also the better‐characterized bone marrow‐derived MSC (BM‐MSC). MC‐MSC proliferated faster, with significantly faster doubling times reaching passage one 8.8 days sooner and surviving longer in culture than WJ‐MSC. All MSC retained the safety aspect of reducing telomere length with increasing passage number. MSC were also assessed for their ability to suppress T‐cell proliferation and for the production of key markers of pluripotency, embryonic stem cells, tolerogenicity (CD40, CD80, CD86 and HLA‐DR) and immunomodulation (indoleamine 2,3‐dioxygenase [IDO] and HLA‐G). The MC‐MSC population displayed all of the positive attributes of WJ‐MSC and BM‐MSC, but they were more efficient to obtain and underwent more population doublings than from WJ, suggesting that MC‐MSC are promising candidates for allogeneic cell therapy in regenerative medicine.

Highlights

  • Mesenchymal stromal cells (MSC) from umbilical cords are of increasing interest for cell therapy for many areas of regenerative medicine, including the treatment of degenerative musculoskeletal disorders, as they are well-supported by medical ethics and are reported to contain immune privileged cells, rendering them potentially suitable for allogeneic therapies [1]

  • Whilst longer doubling times of bone marrow MSC (BM-MSCs) compared to Umbilical cord Mesenchymal Stem cells (UC-MSC) has been reported by other groups [14], our doubling times may be longer than that reported by other centres, since our group have not added any specific growth factors

  • The differences in growth rate between whole cord MSC (MC-MSC) and Wharton’s jelly MSC (WJ-MSC) shown in Figure 1.A may reflect heterogeneity of cells in cultures of MC-MSC, with a combination of different populations of cells possibly supporting better growth, in contrast to cells isolated from a single tissue source such as Wharton’s jelly (WJ)

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Summary

Introduction

Mesenchymal stromal cells (MSC) from umbilical cords are of increasing interest for cell therapy for many areas of regenerative medicine, including the treatment of degenerative musculoskeletal disorders, as they are well-supported by medical ethics and are reported to contain immune privileged cells, rendering them potentially suitable for allogeneic therapies [1]. The use of autologous cells for cell therapies has perceived advantages related to low risk of immune rejection. The use of MSC as an allogeneic treatment in the clinic may only be possible if they proliferate well enough in culture at a low passage number to create cell banks. The proliferative capacity of MSC at low passage may be critical to forming useful cell banks since there are recent reports that BM-MSC at high passage number

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