Umbilical Cord Versus Bone Marrow-Derived Mesenchymal Stromal Cells

Abstract

incetheplacentaisapostnatal tissue and discarded asmedical waste, harvesting stem cells from this organrepresents a noninvasive and ethically conductive proce-dure. Perinatal stem cells isolated from amnion, chorion,umbilical cord, and cord blood are increasingly viewedas reliable sources of mesenchymal stromal cells (MSCs)alternative to bone marrow-derived ones (BM-MSCs),which are currently the most commonly used in clinicalapplications [1–5].Perinatal stem cells are a bridge between embryonic stemcells (ESCs) and adult stem cells (such as BM-MSCs). Theyshare many characteristics of both cells [1,6]. Considering thestructural complexity of the term ‘‘placenta,’’ we have fo-cused our attention on umbilical cord stem cells (UCSCs).Like BM-MSCs, UCSCs possess the fibroblast-like morphol-ogy, nonhematopoietic cell surface phenotypes, low immu-nogenicity, and multipotent differentiation ability [3,5–8].However, there are many differences between UCSCs andBM-MSCs. First, without the ethical cloud, stem cells areeasily harvested from the UC, and the cells have a higherfrequency of proliferation and colony-forming units (CFU)formation than BM-MSCs [9,10]; senescent BM-MSCs wererecorded earlier than UCSCs during subculturing [11]. Sec-ond, beyond MSCs markers, several ESCs markers werepresent in UCSCs, but not to the same extent in BM-MSCs.UCSCs expressed TRA-1-60, TRA-1-81, SSEA-1, SSEA-3,SSEA-4, Oct-4, alkaline phosphatase (ALP), DNMT3B, andGABRB3 [12,13], but showed low expression levels of genesassociated with teratomas formation [14]. These expressionpatterns contribute to justify the observed multipotency ofUCSCs at the molecular level, which may readily cross germlayer boundaries in the differentiation process [15,16]. Third,UCSCs possessed the differentiation to adipogenic, osteo-genic, and chondrogenic lineages [17,18]. When incubated inan adipogenic medium and stained with Oil Red O, UCSCsreadily differentiated into multilocular adipocyte-like cells[10,19–21], while a unilocular lipid droplet was generally seenin the mature adipocytes or BM-MSCs after induction. Hence,the adipogenic capacity of UCSCs was lower than that of BM-MSCs. Also, the lower osteogenesis ability of UCSCs wasdocumented, suggesting that BM-MSC comparatively possess abetter osteogenic potential [22,23], while UCSCs seemed to bemore primitive because they share common genes with ESCs[23]. Interestingly, UCSCs were shown to be nontumorigenic,which suggested that UCSCs are safe for potential clinical ap-plication [24]. Although there are many in vivo studies to de-termine the therapeutic potential, only 2 illustrated thetransplantation of UCSCs in human clinical application withsafe and beneficial results [25,26]. It is clear that many morestudies are essential and necessary. Long-term follow-up isabsolutely needed to validate the feasibility of UCSC-basedtherapy. In summary, according to the minimal criteria of theInternational Society for Cellular Therapy (ISCT) [27], UCSCsgenerally, but not strictly, fulfill the definition of MSCs, as aprimitive stem cell population increasingly used for extensivepreclinical tests and clinical applications.In a recent article published in this journal by Bosch et al.[28], UC-MSCs were isolated and the morphology wasfibroblastic. Although UC-MSCs exhibited a similar expres-sion profile of cell surface proteins compared with BM-MSCs, the cells failed to differentiate into adipo-, osteo-, andchondrogenic lineages [28]. The authors therefore concludedthat this cell population should not be regarded as MSCs. Asmentioned above, it is known that UCSCs possess a loweradipogenic and osteogenic differentiation ability with respectto BM-MSCs, but in this study no typical mesenchymal dif-ferentiation potential was found. In our opinion, the fol-lowing reasons should be considered to provide a betterinterpretation of the results, in light of the published articlessupporting the UC-MSCs differentiation capacity.First, the case for adipogenic differentiation showed thatin the authors’ hands the extent of differentiation of BM-MSCs was up to 6.54% (assessed by the measurement ofareas of lipid vacuoles). This is a strikingly low efficiency,obtained for a cell type that is supposed to constitute thereference for all other MSCs. Therefore, the possibility that