Implantation of osteogenic differentiated donor mesenchymal stem cells causes recruitment of host cells

Abstract

The interaction between host and donor cells is believed to play an important role in osteogenesis. However, it is still unclear how donor osteogenic cells behave and interact with host cells in vivo. The purpose of this study was to track the interactions between transplanted osteogenic cells and host cells during osteogenesis. In vitro migration assay was carried out to investigate the ability of osteogenic differentiated human mesenchymal stem cells (O-hMSCs) to recruit MSCs. At the in vivo level, O-hMSCs were implanted subcutaneously or into skull defects in severe combined immunodeficient (SCID) mice. New bone formation was observed by micro-CT and histological procedures. In situ hybridization (ISH) against human Alu sequences was performed to distinguish donor osteogenic cells from host cells. In vitro migration assay revealed an increased migration potential of MSCs by co-culturing with O-hMSCs. In agreement with the results of in vitro studies, ISH against human Alu sequences showed that host mouse MSCs migrated in large numbers into the transplantation site in response to O-hMSCs. Interestingly, host cells recruited by O-hMSCs were the major cell populations in newly formed bone tissues, indicating that O-hMSCs can trigger and initiate osteogenesis when transplanted in orthotopic sites. The observations from this study demonstrated that in vitro induced O-hMSCs were able to attract host MSCs in vivo and were involved in osteogenesis together with host cells, which may be of importance for bone tissue-engineering applications.

Inflammatory Microenvironment Changes the Secretory Profile of Mesenchymal Stem Cells to Recruit Mesenchymal Stem Cells

“…For wound healing, the mobilization and homing of endogenous MSCs to the injured tissue is an essential but extremely complex process, and the molecular mechanisms are almost unknown [3,4]. In the present study, we demonstrated that cultured hBMSCs exhibited a potent capacity of attracting hBMSCs by secreting soluble chemokines, which was consistent with previous in vivo studies [3,6,7]. Such chemotactic power was comparable to that elicited by IL-1β, IL-6, and TNF-α, further validating the paracrine effects of transplanted MSCs.…”

“…This notion is further reinforced by our previous findings that bone repair mediated by transplanted MSCs was largely attributed to the expansion and differentiation of endogenous MSCs [5]. Moreover, emerging new findings suggested that transplanted donor MSCs could recruit host stem/progenitor cells to the transplantation site for tissue repair [6,7]. These observations have kindled much interest in mechanisms governing host MSCs migration induced by transplanted MSCs.…”

“…Initially, their intrinsic multipotent differentiation properties generated the most interest, but more recently, their paracrine effect, which is manifested as the ability to define and manipulate the local microenvironment by releasing various bioactive molecules, is drawing the attention [23]. After local transplantation, donor MSCs interacted with surrounding microenvironment, resulting in recruitment of endogenous progenitor cells into the injury site to facilitate tissue regeneration [4,6,7]. Local inflammatory responses, incited by injury, have predominant responsibilities for host MSCs recruitment, with multiple inflammatory mediators (cytokines, chemokines and other potential chemoattractants) being involved [16].…”

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

“…Increased BV/TV may also result from an indirect effect of the transplanted cells on osteoblast differentiation as demonstrated by the upregulated expression of endogenous genes in transplanted oim that were associated with osteoblast differentiation, including Dmp1, Phex, and Bgn [48][49][50]. Others have also shown an effect of transplantation on endogenous osteoblast activity, for example, transplantation of osteogenic differentiated MSC in SCID mice resulted in increased bone being produced by host cells [66], and endogenous osteoblast numbers were increased after transplantation of term placental stem cells in a SCID-rab mouse model of medullary myeloma-associated bone loss [67]. We also showed upregulation in transplanted oim of endogenous chondrogenesis genes including chondrogenesis regulator Sox9 [38] and Runx2, implicated in chondrocyte maturation through Col10a1 transactivation [68].…”

IL-8 Enhances Therapeutic Effects of BMSCs on Bone Regeneration via CXCR2-Mediated PI3k/Akt Signaling Pathway

“…The role of seed cells in the process of osteogenesis has been thought to stem from the proliferation and differentiation into osteoblasts by the seed cells on the tissue engineering bone to complete the bone repair [12][13][14][15]. However, recent studies showed that the seed cells contributed less to the later repaired tissues and most cells that participate into bone repair were derived from the host cells that had migrated to the site of injury to promote wound healing [13,[16][17][18].…”