Injectable hydrogel delivery plus preconditioning of mesenchymal stem cells: exploitation of SDF‐1/CXCR4 axis toward enhancing the efficacy of stem cells' homing

Abstract

Clinical applications of mesenchymal stem cells (MSCs) rely on their capacity to home and engraft in the appropriate target injury tissues for the long term. However, their homing efficiency has been observed to be very poor because of the lack or modifications of homing factors SDF-1α and CXCR4 receptors. Hence, this study was designed to investigate the homing and retention of pretreated human adipose tissue-derived MSCs (hASCs) from three different delivery routes in response to SDF-1α, released from chitosan-based injectable hydrogels. After stimulation of ASCs with a hypoxia mimicking agent, the expression level and functionality of CXCR4 were analyzed by flowcytometric analysis (FACS), transwell migration assay and qPCR. Then, the homing/retention of pretreated DiI-labeled hASCs were compared through three different in vivo delivery routes, 2 weeks after transplantation in Wistar rats. The cells were tracked histologically by fluorescent microscope and by PCR for human-specific CXCR4 gene. Results showed CXCR4 has dynamic expression pattern and pretreatment of hASCs significantly up-regulates CXCR4, leading to an increase in migration capacity toward 100 ng/mL SDF-1α in vitro and homing into the subcutaneously implanted hydrogel releasing SDF-1α in vivo. Furthermore, it seems that SDF-1α is particularly important in the retention of ASCs, in addition to its chemoattraction role. In summary, the delivery route in which the ASCs were mixed with the hydrogel rather than systemic delivery and local injection and preconditioning undertaken to increase CXCR4 expression concomitant with SDF-1α delivery by the injectable hydrogel, allowed for further homing/retention of ASCs. This might be a promising way to get better therapeutic outcomes in stem cell therapy.

Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4

“…We used matrigel to establish a controlled release of SDF-1α, which is necessary to form a gradient induced migration of MSCs [32]. Matrigel plugs mixed with or without SDF-1α were subcutaneously implanted on the right and left dorsal side of NOD/SCID mice respectively.…”

“…MSCs from AT (AT-MSCs) were isolated using the method described previously [32]. Briefly, lipo-aspirates were washed three or four times with medium and incubated with 0.2% collagenase for 120 minutes at 37 °C with gentle agitation in a shaking water bath.…”

“…In-vivo assessment of MSC migration was performed using a modified matrigel plug assay as described previously [32]. NOD/SCID mice were divided into five groups: control-uninjected, untreated BM-MSCs, IL-3-treated BM-MSCs, untreated AT-MSCs and IL-3-treated AT-MSCs ( n  = 6 per group).…”

A Hyper-Crosslinked Carbohydrate Polymer Scaffold Facilitates Lineage Commitment and Maintains a Reserve Pool of Proliferating Cardiovascular Progenitors

“…62 Paracrine factors enhance neovascularization and reduce cell death. Recently, a swine model of an acute myocardial infarction demonstrated improved clinical outcomes after IGF-1 and HGF administration 63 due to a reduction in pathologic tissue growth (fibroblast proliferation) and an induction of myocardial regeneration.…”

Standardized Sophora pachycarpa Root Extract Enhances Osteogenic Differentiation in Adipose‐derived Human Mesenchymal Stem Cells

“…Lipoaspirate wastes of healthy donors undergoing esthetic surgery were used to isolate ADMSCs according to the protocol developed by Naderi‐Meshkin et al (). According to the Ethics Committee of Mashhad University of Medical Sciences, written informed consents were obtained from donors of lipoaspirates.…”