HOX and TALE signatures specify human stromal stem cell populations from different sources

Abstract

Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues.

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

“…As the adipose tissue can be found in abundance with reduced donor site morbidity, the problems associated to bone marrow harvesting could be overcome. Following our observation that MSCs from different sources display different expression profiles of the homogenes of HOX and TALE subfamilies [16], we analyzed here MSCs derived from different sources for proliferative and differentiating properties in vitro, in the light of their possible clinical applications. In particular, vertebral bone marrow is rich in MSCs, such as iliac crest bone marrow.…”

“…We previously investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues [15]. We observed that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures [16]. Our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutic strategies for regeneration and repair of specific tissues.…”

Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells

“…Although MSCs were first discovered in BM, other tissuespecific MSCs have been recently identified and categorized on the basis of their antigen expression signatures and cell differentiation spectra. Tissue-specific MSCs partly overlap with pericytes and span aubiquitous distribution in human tissues as structural cells [24,30]. We first isolated and characterized, through four lineages, MSCs in bone marrow [33].…”

“…We first isolated and characterized, through four lineages, MSCs in bone marrow [33]. Subsequently, we isolated and banked tissuespecific MSCs from amnion, foetal liver, tonsil, dental pulp, lung, bowel [24,30] and dermal connective tissue. Colonic (C-) MSCs were subjected to in depth analysis and comparison to BM-MSCs, classified, both functionally and by smooth muscle actin expression, in peri-cryptic and inter-cryptic myofibroblasts [24,30].…”

“…Subsequently, we isolated and banked tissuespecific MSCs from amnion, foetal liver, tonsil, dental pulp, lung, bowel [24,30] and dermal connective tissue. Colonic (C-) MSCs were subjected to in depth analysis and comparison to BM-MSCs, classified, both functionally and by smooth muscle actin expression, in peri-cryptic and inter-cryptic myofibroblasts [24,30]. Apical peri-cryptic myofibroblasts are in close contact with intestinal epithelial stem cells, wherein they nurture, regulate and maintain them in the intestinal niche, similarly to the hematopoietic niche in the BM.…”