Editors' ChoiceRegenerative Medicine

Fighting for their lives: A strategy for improved cell transplantation survival

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Science Translational Medicine  07 Mar 2018:
Vol. 10, Issue 431, eaar7536
DOI: 10.1126/scitranslmed.aar7536

Abstract

Slow release of pro-survival peptides from collagen biomaterials improves stem cell engraftment following transplantation in a mouse model of ischemia.

Stem cell–based therapies are very promising for regenerative medicine due to their ability to secrete growth factors, participate in immunomodulation, and differentiate into a wide range of cell types. Nonetheless, clinical application of stem cell–based therapies has been severely limited due to poor cell survival and engraftment after donor cell delivery. Ongoing research is investigating methods for improving cell survival following transplantation. One approach is to use biomaterials to mimic the native cellular microenvironment, resulting in prolonged stem cell survival and in the ability to control stem cell fate. Previous research has also shown that co-delivery of stem cells with growth factors can improve engraftment; however, this approach is limited by the short half-lives of full-length growth factors. Here, Lee and colleagues developed and tested in rodent models of ischemia an injectable collagen biomaterial cross-linked with pro-survival peptides to improve stem cell engraftment.

Peptide analogs of full-length proteins are advantageous, as they maintain the same or partial biological activity with improved stability and at a lower cost. Here, the peptide analogs of proteins shown to improve survival of transplanted stem cells—specifically bone morphogenetic protein-2, erythropoietin, and fibroblast growth factor-2—were cross-linked to collagen and co-injected with stem cells in vivo in mice. Two murine models were investigated: bone marrow mononuclear cell delivery in a hind limb ischemia model and cardiac progenitor cell delivery in a myocardial infarction model. In both animal models, the slow release of pro-survival peptides cross-linked within collagen successfully resulted in improved stem cell engraftment and cell survival compared with cells injected without the pro-survival peptides conjugated to collagen.

Prolonged cell survival is critical for the successful translation of stem cell transplantation therapies. Here, the authors demonstrate long-term cell survival following transplantation into an ischemic microenvironment via delivery from a collagen matrix cross-linked with pro-survival peptides. It remains to be seen if the proposed approach will be effective in larger, more clinically relevant animal models; nonetheless, Lee et al.'s work is a promising first step toward improving donor stem cell survival following transplant.

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