Identity and ranking of colonic mesenchymal stromal cells

Abstract

Although ongoing clinical trials utilize systemic administration of bone-marrow mesenchymal stromal cells (BM-MSCs) in Crohn's disease (CD), nothing is known about the presence and the function of mesenchymal stromal cells (MSCs) in the normal human bowel. MSCs are bone marrow (BM) multipotent cells supporting hematopoiesis with the potential to differentiate into multiple skeletal phenotypes. A recently identified new marker, CD146, allowing to prospectively isolate MSCs from BM, renders also possible their identification in different tissues. In order to elucidate the presence and functional role of MSCs in human bowel we analyzed normal adult colon sections and isolated MSCs from them. In colon (C) sections, resident MSCs form a net enveloping crypts in lamina propria, coinciding with structural myofibroblasts or interstitial stromal cells. Nine sub-clonal CD146(+) MSC lines were derived and characterized from colon biopsies, in addition to MSC lines from five other human tissues. In spite of a phenotype qualitative identity between the BM- and C-MSC populations, they were discriminated and categorized. Similarities between C-MSC and BM-MSCs are represented by: Osteogenic differentiation, hematopoietic supporting activity, immune-modulation, and surface-antigen qualitative expression. The differences between these populations are: C-MSCs mean intensity expression is lower for CD13, CD29, and CD49c surface-antigens, proliferative rate faster, life-span shorter, chondrogenic differentiation rare, and adipogenic differentiation completely blocked. Briefly, BM-MSCs, deserve the rank of progenitors, whereas C-MSCs belong to the restricted precursor hierarchy. The presence and functional role of MSCs in human colon provide a rationale for BM-MSC replacement therapy in CD, where resident bowel MSCs might be exhausted or diverted from their physiological functions.

Vitamin K2 and its Impact on Tooth Epigenetics

“…The International Society for Cellular Therapy has released a position statement wherein they list three criteria to define human stem cells: (1) adherence to plastic, (2) specific surface antigen expression, and (3) multipotent differentiation potential [83]. The cells to be used in this project fulfil all three criteria [84], and were isolated in accordance with a published procedure described by Sorrentino et al [85].…”

Mesenchymal Stem Cells Manage Endogenous Tissue Regeneration

“…(84) MSCs reside in local epithelial niches in close proximity to capillary walls. (85,86) They might provide a life-long regenerative reservoir of new cells such as myofibroblasts (87), as well as macrophages (102,131 (133) Substantial advancement has been made recently in the understanding of the interactions between MSCs and immune cells. As a result of such studies, now MSCs are considered to intuitively respond to their immediate environment and to adapt their response accordingly through the release of soluble factors such as PGE2, kyneurenine, IL-10, TNF-stimulated gene 6 protein (TSG-6), NO, and transforming growth factor (TGF-b)-1 (134)(135)(136)(137)(138)(139) and/ or through cell contact signaling such as Notch, and CD95/Fas (140)(141)(142).…”

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

“…hematopoietic stem cells (HSCs). MSCs are endowed with extensive proliferation, equal or longer than three months in vitro, the ability to differentiate in at least four structural lineages, osteoblasts, chondroblasts, adipoblasts and reticular stromal cells supporting HSCs; the capability to produce huge amounts of multiple growth factors [33,37] underlying their anti-apoptotic, immuneregulator, nurturing and regenerative potential [30,33,37]. 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.…”

“…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].…”