Recruitment of Endogenous Stem Cells for Tissue Repair

Abstract

The traditional concept of stem cell therapy envisions the isolation of stem cells from patients, propagation and differentiation in vitro, and subsequent re-injection of autologous cells into the patient. There are many problems associated with this paradigm, particularly during the in vitro manipulation process and the delivery and local retention of re-injected cells. An alternative paradigm that could be easier, safer, and more efficient, would involve attracting endogenous stem cells and precursor cells to the defect site for new tissue regeneration. Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin, exerts a strong chemoattractive effect on mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and induces migration of MSCs in vitro. However, HGF undergoes rapid proteolysis in vivo, which results in a very short lifetime of the bioactive cytokine. To maintain the therapeutic level of HGF at the defect site necessary for endogenous stem cell recruitment, sustained, long-term, and localized delivery of HGF is required. Thiol-modified glycosaminoglycans hyaluronan (HA) and heparin (HP), combined with modified gelatin (Gtn), have been crosslinked with poly(ethylene glycol) diacrylate (PEGDA) to afford semisynthetic ECM-like (sECM) hydrogels that can both provide controlled growth factor release and permit cell infiltration and proliferation. Herein we compare the use of different sECM compositions for controlled release of HGF and concomitant recruitment of human bone marrow MSCs into the scaffold in vitro. [Figure: see text].

Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds

“…[35][36][37] Several methods have previously been used to recruit endogenous progenitor cells, including injection of cytokines involved in stem cell homing, such as SDF or HGF, and gene therapy. 32,38 Polymeric hydrogels seeded with stem cells, however, display several advantages over these methods. Hydrogels promote sustained expression of cytokines involved in progenitor cell recruitment, rather than the transitory increase achieved through injection, and they avoid the safety concerns involved in gene therapy, such as the use of viral vectors and the regulation of transgene expression after completing therapeutics.…”

Hepatic differentiation from human mesenchymal stem cells on a novel nanofiber scaffold

“…Human mesenchymal stem cells (hMSCs) [8] as well as human embryonic stem cells (hESC) [9], liver stem cells/oval cells [10], cord blood cells [11], bone marrow stem cells [12] and fetal hepatocytes [13] are stem cell types that display potential to develop into hepatocytes. Bone marrow represents an abundant and accessible source of adult stem cells that can differentiate along multiple lineage pathways, including the hepatic lineage [14][15][16][17]. Both hematopoietic stem cells (HSCs) and MSCs have the capacity to transdifferentiate into hepatocytes in vivo [14,15]; it appears that MSCs are the most potent component of bone marrow cells in hepatic differentiation [15].…”

“…The traditional concept of stem cell-based therapy consists of the isolation of stem cells from patients, expansion and differentiation in vitro, and subsequent re-transplantation of autologous cells into the patient. There are many problems associated with this paradigm, particularly during the in vitro manipulation process and the delivery and local engraftment of re-transplantation cells [16]. Moreover, stem cell fate is influenced by a number of factors including extracellular matrices (ECMs) and interactions that require robust control for safe and effective regeneration of functional tissue [19].…”

Integration of the Neural Stem and Progenitor Cells into Existing Neuronal Circuitry and Adult Neurogenesis in the Dentate Gyrus of the Hippocampus

“…The important advantages of the endogenous NSCs including lack of need to external cell source, devoid of ethical and political considerations, as well as without risk of tumorigenicity and rejection possibilities. Also, access to endogenous NSCs is much easier, simpler and more effective than exogenous stem cells [11,33]. After any kind of injury to the CNS, the endogenous NSCs are recruited to the lesion site, but this natural response is often insufficient and unsatisfactory for recovery of the functional deficits [34][35][36][37].…”