Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy

Abstract

Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies.

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

“…Adult stem cells are promising sources for tissue regeneration but present challenges by becoming senescent during ex vivo expansion as well as having a harsh environment for transplantation. An increasing number of studies on preconditioning strategies to refine ex vivo expansion microenvironment for promoting engraftment [155], homing [156], and viability [157–159] after stem cell transplantation, particularly for cardiac tissue regeneration [155,159], have been published. Different from the above-mentioned strategies for cell preconditioning, this paper, for the first time, summarizes and assesses current efforts at altering the ex vivo microenvironment via hypoxia, soluble factors, and/or dECM to improve stem cell survival and chondrogenic potential post-transplantation.…”

Perivascular cells and tissue engineering: Current applications and untapped potential

“…So far, the majority of preclinical studies and clinical trials have focused on the delivery of cells suspensions by injection in the area of damage; however, the benefits of cell therapy have been limited by the poor survival and rapid removal of cells (Naderi-Meshkin, Bahrami, Bidkhori, Mirahmadi, & Ahmadiankia, 2015). Evidence shows that the injected cells do not contribute to the reconstitution of the damaged tissue, highlighting the urgency of new solutions for organ/tissue replacement.…”

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

“…Human MSCs exposed to hypoxic preconditioning have shown increased mobility and therapeutic potential compared to unconditioned control cells [63,64] . The expression levels of CXCR4, CXCR7, CX3CR1, SDF-1a, and integrin αM [64][65][66][67] increased when MSCs were exposed to hypoxic conditions. Although the underlying mechanism is not completely clear, hypoxia-inducible factor-1 alpha (HIF-1α) is considered the master regulator of the adaptive response to hypoxia [68] .…”

“…The native CD44 glycoform on MSCs can be converted to a ligand for E-selectin by treatment with a-1,3-fucosyltransferase under specific enzymatic conditions without affecting cell viability or multipotency. Such modification of CD44 with an E-selectin binding motif increased specific homing of MSC to the BM [50,65] . While cell surface engineering is a novel method to enhance migration in a controlled manner, the cost of this technique is elevated.…”