Journey of Mesenchymal Stem Cells for Homing: Strategies to Enhance Efficacy and Safety of Stem Cell Therapy

Abstract

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and the in vivo environment facilitate and are required for the migration of MSCs to the site of insult or injury in vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.

The Effect of Granulocyte-colony Stimulating Factor on Rotator Cuff Healing After Injury and Repair

“…Lastly, we did not perform an analysis of the mobilization effect of subcutaneous G-CSF administration or a phenotypic study of the cells that were recruited to the surgical site. The effect of G-CSF administration on stem cell mobilization is well established in murine and other models [11,22,28,35,37,46].…”

“…Once in circulation, chemokine-mediated signaling causes MSCs and HSCs to ''migrate'' to capillary beds near the site of injury, adhere to the inner epithelial layers, and then ''transmigrate'' into the injured tissue to participate in regenerative processes [49]. Numerous cytokines and small molecule receptor antagonists have been shown to induce bone marrow mobilization to increase circulating stem cell concentration [28], one of which is granulocyte-colony stimulating factor (G-CSF), a glycoprotein known to participate in the native immune response [48]. G-CSF is used clinically to combat neutropenia in patients undergoing myeloablative procedures [45] and for HSC mobilization in bone marrow donation [1,46].…”

A novel approach of human embryonic stem cells therapy in treatment of Friedrich's Ataxia

“…Neurons and cardiomyocytes are the two affected cell types in FRDA [8]. As human stem cells have ability to migrate and home to the injury site [15], we could assume that hESCs might have also migrated to the affected brain and differentiated into neurons and cardiomyocytes. The size of the hESCs used in our study was < 1 µm, so it can be assumed that hESCs have permeated through the parenchyma via blood brain barrier.…”

The role of the microenvironment on the fate of adult stem cells

“…Therefore, plastic SCs and progenitor cells have been studied in a variety of environments and have been produced through physical, chemical, genetic, and pharmacological manipulations. In suitable microenvironments, plastic SCs generally have improved cell survival, increased neuronal differentiation, and enhanced paracrine effects, leading to increased trophic support, improved homing to the lesion site, and intensive suppression inflammatory factors and immune responses to promote functional recovery (Figure 2) [60,61]. The microenvironment serves to drive the cells into a state of readiness in different environments.…”

“…The factors released upon tissue damage or apoptosis mobilize and recruit stem and progenitor cells to the damaged site, where they proliferate and differentiate, eventually replacing the damaged tissues [60]. To respond to migratory signals released in the sites of injury, the SCs must express surface receptors capable of sensing those signals.…”