Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization

Abstract

Implanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10+ adult stem cells contribute to both encapsulation and microvessel formation. Sox10+ adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10+ stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10+ stem cells to myofibroblasts could be recapitulated in vitro. On the other hand, Sox10+ stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10+ stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10+ stem cells. Transplanted Sox10+ stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination.

Sox10 + Cells Contribute to Vascular Development in Multiple Organs—Brief Report

“…3–5, 10–14 In recent years, accumulating studies showed that Sox10+ stem cells exist in multiple adult tissues and participate in tissue remodeling, including spinal cord, 12 inferior turbinate, 22 periodontal ligament, 23 hair follicle, 24, 25 mammary epithelium, 26 bone marrow, 27 blood vessel walls 19–21, 28 and subcutaneous loose connective tissues. 29 Moreover, Sox10 also plays a role in tumor formation of melanoma. 30 Lineage tracing and advanced imaging techniques have been widely used to study cell differentiation during development.…”

Adult Stem Cells in Vascular Remodeling

“…In our recent work, we found Sox10 + stem cells in the stroma of subcutaneous connective tissues which had the same properties as MVSCs in large vessels 24 , 25 . These Sox10 + stem cells are precursors of pericytes and fibroblasts, as described in the previous section, and contribute to both fibrosis and microvessel formation during tissue repair and regeneration 24 . Gli1 + stem cells had similarly wide distribution as the Sox10 + stem cells and were found in the perivascular space and also adventitial layer of large arteries.…”

“…Notably, most of these foam cells are initially derived from preexisting intimal-resident myeloid progenitors rather than recently recruited blood monocytes 23 . In addition, the inflammatory cells activate medial SMCs and stem cells, prompting adventitial stem cells to proliferate and migrate into the intima, where they may differentiate and also obtain some properties of myofibroblasts and macrophages 3 , 20 - 22 , 24 , 25 . Disease proceeds as the abnormal vascular wall processes prompt macrophages, together with leukocytes, activated ECs, and SMCs, to secrete increasing amounts of inflammatory cytokines to recruit more inflammatory cells from the circulation and resident adventitial tissues.…”

“…1 ). In wound healing and scar formation, MVSC-like Sox10 + cells (which are also found in soft tissues around blood vessels and throughout the body) can differentiate into both myofibroblasts and SMCs 24 . Following the implantation of polymer vascular grafts for instance, these cells, rather than SMCs, are recruited to the outer surface of the grafts and gradually differentiate into SMCs 70 , recapitulating some aspect of vascular development.…”

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

“…Three-layered spheroids are obtained through the application of external magnetic fields. [136][137][138][139][140] However, Matrigel is limited to in vitro applications, since it derives from the Engelbreth-Holm-Swarm (EHS) sarcoma. Adapted with permission.…”