Abstract
Mesenchymal stromal stem cells (MSC) that reside in the bone marrow (BM) can be amplified in vitro. In 2-dimension (D) cultures, MSC exhibit a morphology similar to fibroblasts, are able to inhibit T lymphocyte and natural killer cell proliferation, and can be differentiated into adipocytes, chondrocytes, or osteoblasts if exposed to specific media. Here we show that medullar MSC cultured in 2D formed an adherent stroma of cells expressing well-organized microfilaments containing α-smooth muscle actin and nonmuscle myosin heavy chain IIA. MSC could be grown in 3D in collagen membranes generating a structure which, upon exposition to 50 mM KCl or to an alternating electric current, developed a contractile strength that averaged 34 and 45 μN/mm2, respectively. Such mechanical tension was similar in intensity and in duration to that of human placenta and was annihilated by isosorbide dinitrate or 2,3-butanedione monoxime. Membranes devoid of MSC did not exhibit a significant contractility. Moreover, MSC nested in collagen membranes were able to control T lymphocyte proliferation, and differentiated into adipocytes, chondrocytes, or osteoblasts. Our observations show that BM-derived MSC cultured in collagen membranes spontaneously differentiate into contractile myofibroblasts exhibiting unexpected properties in terms of cell differentiation potential and of immunomodulatory function.
Highlights
Mesenchymal stromal stem cells (MSC) can be derived from almost any vascularized tissue of the organism after in vitro amplification with media supplemented with foetal calf serum, platelet-derived growth factor (PDGF), or human platelet lysate (HPL) [1,2,3,4]
In this study we assessed whether the phenotype of MSC derived from human bone marrow was compatible with a pericyte origin, and because several studies reported that myofibroblasts may originate from pericytes [11, 12], if MSC could differentiate into contractile myofibroblast in vitro
While the majority if not the totality of cells cultured with HPL expressed α-smooth muscle actin (αSMA) (see Figure 1(b)), our investigations showed that MSC laden in the membranes were simultaneously endowed with the ability to differentiate into chondrocytes, osteoblasts, or adipocytes, and prevented allogenic T lymphocyte proliferation
Summary
Mesenchymal stromal stem cells (MSC) can be derived from almost any vascularized tissue of the organism after in vitro amplification with media supplemented with foetal calf serum, platelet-derived growth factor (PDGF), or human platelet lysate (HPL) [1,2,3,4]. The identification of the in vivo counterpart of MSC has been rather difficult to achieve because MSC precursors are scarce in vivo [5, 6]. For this reason in vitro amplification of MSC is generally required prior to any investigation. The media used to amplify MSC in vitro contain various biologically active factors including transforming growth factor-β (TGF-β), Stem Cells International
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