In SituTissue Regeneration: Chemoattractants for Endogenous Stem Cell Recruitment

Abstract

Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

“…In contrast to cell transplantation, the present strategy of endogenous regeneration upon spatiotemporal release of two recombinant human proteins offers a ready-to-implant graft that may serve as a therapeutic prototype. Regeneration by cell homing, now being sporadically demonstrated in several tissue/organ systems (12, 13, 19), provides an alternative to cell transplantation. Biologically, regeneration by cell transplantation or cell homing is not mutually exclusive.…”

“…Equilibrium friction coefficients, µeq, on angular velocity were measured to estimate the scaffold’s frictional property (19). Cylindrical samples (10-mm diameter × 3-mm thickness), prepared from the middle region of menisci and scaffolds, were fixed to an impermeable bottom platen using cyanoacrylate glue and immersed in a PBS bath.…”

“…Using unconfined compression, samples were preconditioned with 15 cycles of 0 to 5% compressive strain, followed by stress relaxation with 20% compressive strain. A Kelvin standard solid viscoelastic model was applied to calculate instantaneous modulus (E i ), modulus of relaxation ( E r ), and viscosity (µ) (19, 24). …”

Advancing the cellular and molecular therapy for intervertebral disc disease

“…In the course of a natural healing response, the affected cells and tissues release signals attracting progenitor cells from their niches to the injury site. The specific chemo-attractant molecules depend on the tissue to repair and include a variety of growth factors, cytokines and chemokines [117]. Mesenchymal stem cells express receptors for a majority of these chemokines and are capable of producing themselves further chemotactic factors upon stimulation.…”

Harnessing endogenous stem/progenitor cells for tendon regeneration

“…Current stem cell-based regenerative therapies predominantly involve isolation and sorting, ex vivo culture expansion, and transplantation with or without directed differentiation (1)(2)(3)(4). Despite being a valid approach, cell transplantation has encountered crucial barriers in therapeutic translation, including immune rejection; pathogen transmission; potential tumorigenesis; issues associated with packaging, storage, and shipping; and difficulties in clinical adoption and regulatory approval (2,(5)(6)(7)(8).…”