LETTER TO THE EDITOR Umbilical Cord Versus Bone Marrow-Derived Mesenchymal Stromal Cells Yong-Can Huang, 1,2 Ornella Parolini, 3 Giampiero La Rocca, 4,5 and Li Deng 1 S ince the placenta is a postnatal tissue and discarded as medical waste, harvesting stem cells from this organ represents a noninvasive and ethically conductive proce- dure. Perinatal stem cells isolated from amnion, chorion, umbilical cord, and cord blood are increasingly viewed as reliable sources of mesenchymal stromal cells (MSCs) alternative to bone marrow-derived ones (BM-MSCs), which are currently the most commonly used in clinical applications [1–5]. Perinatal stem cells are a bridge between embryonic stem cells (ESCs) and adult stem cells (such as BM-MSCs). They share many characteristics of both cells [1,6]. Considering the structural 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 and BM-MSCs. First, without the ethical cloud, stem cells are easily harvested from the UC, and the cells have a higher frequency of proliferation and colony-forming units (CFU) formation than BM-MSCs [9,10]; senescent BM-MSCs were recorded earlier than UCSCs during subculturing [11]. Sec- ond, beyond MSCs markers, several ESCs markers were present 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, and GABRB3 [12,13], but showed low expression levels of genes associated with teratomas formation [14]. These expression patterns contribute to justify the observed multipotency of UCSCs at the molecular level, which may readily cross germ layer boundaries in the differentiation process [15,16]. Third, UCSCs possessed the differentiation to adipogenic, osteo- genic, and chondrogenic lineages [17,18]. When incubated in an adipogenic medium and stained with Oil Red O, UCSCs readily differentiated into multilocular adipocyte-like cells [10,19–21], while a unilocular lipid droplet was generally seen in 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 was documented, suggesting that BM-MSC comparatively possess a better osteogenic potential [22,23], while UCSCs seemed to be more 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 the transplantation of UCSCs in human clinical application with safe and beneficial results [25,26]. It is clear that many more studies are essential and necessary. Long-term follow-up is absolutely needed to validate the feasibility of UCSC-based therapy. In summary, according to the minimal criteria of the International Society for Cellular Therapy (ISCT) [27], UCSCs generally, but not strictly, fulfill the definition of MSCs, as a primitive stem cell population increasingly used for extensive preclinical tests and clinical applications. In a recent article published in this journal by Bosch et al. [28], UC-MSCs were isolated and the morphology was fibroblastic. 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-, and chondrogenic lineages [28]. The authors therefore concluded that this cell population should not be regarded as MSCs. As mentioned above, it is known that UCSCs possess a lower adipogenic and osteogenic differentiation ability with respect to 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 better interpretation of the results, in light of the published articles supporting the UC-MSCs differentiation capacity. First, the case for adipogenic differentiation showed that in the authors’ hands the extent of differentiation of BM- MSCs was up to 6.54% (assessed by the measurement of areas of lipid vacuoles). This is a strikingly low efficiency, obtained for a cell type that is supposed to constitute the reference for all other MSCs. Therefore, the possibility that 1 Laboratory of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China. 2 Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’ Republic of China. 3 Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy. 4 Sezione di Anatomia Umana, Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Universita ` degli Studi di Palermo, Palermo, Italy. 5 Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy. STEM CELLS AND DEVELOPMENT Volume 21, Number 15, 2012 Ó Mary Ann Liebert, Inc. DOI: 10.1089/scd.2012.0216 2900