Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms

Abstract

The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy. Engraftment and differentiation of exogenous BMDCs could not be detected. Yet CM led to the mobilization and infiltration of endogenous circulating cells into the heart. Cell recruitment was facilitated by the local expression of pro-inflammatory factors such as the macrophage chemoattractant protein-1, interleukin-6, and endothelial adhesion molecules. Consistently, in vitro assays showed that CM increased endothelial adhesiveness to circulating cells by upregulating the expression of adhesion molecules, and stimulated angiogenesis/endothelial tube formation. Overall, our results suggest that both treatments exert vasculoprotective effects on the heart of uremic rats by stimulating endogenous repair mechanisms.

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…This was further confirmed in several other studies showing the increase of c-kit + CSC within the heart tissue after MSC transplantation [354,355]. Recently, the injection of BM-derived MNC conditioned media alone was found to significantly increase the number of circulating Sca-1 + and c-kit + cells and favors the infiltration of beneficial endogenous BMderived cells, indicating paracrine signaling as the prevailing mechanism of resident cell recruitment [356]. Furthermore, SC therapy promoted the activation of epicardium-derived cells and their differentiation into endothelial cells, smooth muscle cells and cardiomyocytes [355].…”

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

“…BMDC are immature, pluripotent hematopoietic stem cells, regulatory T cells, endothelial progenitors and mesenchymal stem cells (MSC), all secreting a variety of growth factors, angiogenetic factors, cytokines and exosomes. The accumulation of BMDC in PMN and subsequent immune suppression, angiogenesis and inflammation, support the settling and growth of tumor cells . MSC may differentiate into well‐characterized stromal cell types such as CAF.…”

Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice

“…Antibody array data gave some insight on the molecular mechanisms of TGFß1 treatment. TGFß1 treatment resulted in significantly lower expression of IL6, MCP1, MMP3, TCK1, KC, and MIP1G which have been previously reported to play a role in inflammation and migration [40][41][42][43]. Inhibition of these paracrine factors by TGFß1 might have resulted in MSCs that lost their migratory property and remained in the testis which might have further contributed to restoring the SSC niche, resulting in a higher donor-derived TFI.…”