Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties

Abstract

BackgroundCell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population.ResultsHuman ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-β, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress.ConclusionBMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-017-0129-9) contains supplementary material, which is available to authorized users.

Isolation and characterization of turkey bone marrow‐derived mesenchymal stem cells

“…The gene expression of TNMD , a well‐known late stage tenogenic marker, was also increased. The increased expression of tendon‐related genes following BMP12 treatment is in good agreement with other studies performed on MSCs from mammals including human, rat, and horse . Therefore, we postulate that there will be no appreciable differences in MSCs tenogenesis when using turkey as an animal model.…”

“…Therefore, we further investigated the tenogenesis of turkey bone marrow‐derived MSCs. BMP12 is a key growth factor involved in guiding MSCs tenogenic differentiation . Previous studies have shown BMP12 provided potent signal for equine BMSCs tenogenic commitment .…”

“…BMP12 is a key growth factor involved in guiding MSCs tenogenic differentiation. 39,40 Previous studies have shown BMP12 provided potent signal for equine BMSCs tenogenic commitment. 39 Stimulated by BMP12 for 14 days, the expression level of MKX, TNMD, and EGR1 was significantly upregulated in turkey bone marrow-derived cells.…”

Comparison of the paracrine activity of mesenchymal stem cells derived from human umbilical cord, amniotic membrane and adipose tissue

“…in chronic tendinopathies), intensified vasculogenesis could be detrimental. 30 Unlike endometrial cells from a non-pregnant uterus, in which VEGF is simultaneously expressed with MMPs, 31 both AM-MSCs and UC-MSCs showed lower MMP-1 and MMP-13 secretion compared to AD-MSCs, and there was a statistically significant difference in MMP-8 production. The increased proteolytic enzymes levels and massive leukocyte influx during the inflammatory process results in tissue destruction.…”

“…On the other hand, in some applications (i.e. in chronic tendinopathies), intensified vasculogenesis could be detrimental …”