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

Abstract

Background/Aims: Human bone-marrow mesenchymal stem cells (hBMSCs) are widely transplanted into inflammatory microenvironment to accelerate tissue regeneration. Transplanted hBMSCs recruit host hBMSCs through a poorly understood mechanism. This study was aimed to determine whether and how inflammatory microenvironment influenced the host-hBMSCs-recruiting capability of transplanted hBMSCs. Methods: Pro-inflammatory factors, including IL-1β, IL-6 and TNF-α, were utilized to mimic inflammatory microenvironment. hBMSCs were cultured and conditioned media (CM) were collected. The effects of inflammatory microenvironment on the host-hBMSCs-recruiting capability of cultured hBMSCs were revealed by transwell migration assays. Employing semi-quantitative and quantitative cytokine antibody assays, we examined the secretory profile of cultured hBMSCs. Results: CM from cultured hBMSCs exerted excellent host-hBMSCs-recruiting capability, which was significantly promoted by exposure to inflammatory microenvironment. Within inflammatory microenvironment, hBMSCs secreted more chemokines related to cell migration. Finally, 21 cytokines were verified as potential factors accounting for the enhanced host-hBMSCs-recruiting capability of cultured hBMSCs exposed to inflammatory microenvironment. Conclusion: These results strongly suggested that in clinic, inflammatory microenvironment might promote the host-hBMSCs-recruiting capacity of transplanted hBMSCs by increasing chemokines secretion. Modulation of such characteristics of hBMSCs might provide novel therapeutic ideas in the context of hBMSCs.

Mesenchymal stem cells promote endothelial progenitor cell migration, vascularization, and bone repair in tissue‐engineered constructs via activating CXCR2‐Src‐PKL/Vav2‐Rac1

“…In this context, implanted MSCs modulate the local microenvironment to stimulate the host's innate regenerative activity via paracrine actions (11). This notion is further reinforced by our finding that the inflammatory microenvironment leads to a massive amplification of the paracrine capacity of MSCs (12). The release of CXC chemokine family members, such as growth-related oncogenes C-X-C motif ligand (CXCL)1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8, is significantly enhanced after inflammatory stimulation.…”

“…We recently reported that implanted donor MSCs could induce the homing of host EPCs to the bone defect site, an initiating event of vasculogenesis (4). Moreover, the release of CXCR2 ligands from MSCs is significantly enhanced in an inflammatory microenvironment (12). Therefore, a major goal for us is to determine the impact of CXCR2-mediated signaling during bone repair induced by TECs.…”

“…Human bone marrow MSCs (hBMSCs) were isolated and cultured as previously described (12). hBMSCs were cultured in basic culture medium containing DMEM/F12 (1:1; Hyclone Laboratories, Logan, UT, USA), 10% FBS, and 100 U/ml penicillin/streptomycin.…”

Adult stem cells in neural repair: Current options, limitations and perspectives

“…This helper profile has been observed in neural stem cells and mesenchymal stem cells. In the case of mesenchymal stem cells, this function can play an important role in changing the macrophage proinflammatory profile into a proregenerating role, once there is no longer an urgent need for a robust immune response [14][15][16] . Understanding the biology of stem cells and their niches, as well as the mechanisms involved in their multipotent state, are basic criteria to achieve great experimental results and to take the next step towards clinical trials.…”

Perspectivas de terapia celular em neurologia

“…Assim como outros tipos de células-tronco, as CTAs são capazes de promover regeneração tecidual por diversos mecanismos. Além de promover repovoamento do tipo celular perdido (seja se diferenciando diretamente nele, ou atraindo CTs no entorno para fazer isso), elas também apresentam potencial imuno-modulador: alguns estudos já comprovaram que elas são capazes de inibir o processo inflamatório local secundário a uma lesão, e estimular a regeneração tecidual 57 . CT mesenquimais, por exemplo, são capazes de mudar o fenótipo dos macrófagos ao serem transplantadas para um tecido lesado, inibindo sua atividade pró-inflamatória e estimulando sua atividade pró-regenerativa 57,58 .…”