A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

Stem Cell Reports. 2015 Jun 9;4(6):1031-45. doi: 10.1016/j.stemcr.2015.04.008. Epub 2015 May 14.

Abstract

The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blindness / genetics
  • Blindness / therapy
  • Blindness / veterinary
  • Cell Survival
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Immunohistochemistry
  • Methylcellulose / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • Retina / cytology
  • Retina / metabolism
  • Retinal Rod Photoreceptor Cells / cytology
  • Rhodopsin / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stroke / chemically induced
  • Stroke / therapy
  • Stroke / veterinary

Substances

  • Hyaluronan Receptors
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hyaluronic Acid
  • Methylcellulose
  • Rhodopsin