Seminars

Abstract

Sickle cell disease (SCD) is an inherited blood disorder that affects millions globally but is significantly under-researched compared to conditions of similar etiologies or disease burden. Bone marrow transplantation is the only known cure for SCD; less than 1% of transplantations have been performed in SCD patients. This is primarily due to an insufficient supply of appropriate donor stem cells compounded by a limited understanding of how the sickle bone marrow microenvironment hinders engraftment. Cell-releasing hydrogel carriers promise to be a transplantation tool that addresses the poor cell retention and viability associated with the clinical standard of intravenous delivery. The work discussed here reports on developing an injectable cell-releasing hydrogel carrier to improve hematopoietic stem cell transplantation efficiency. The poly (ethylene glycol) based hydrogel system recapitulates the biophysical properties of native bone marrow, maintains cell viability post-delivery, and releases hematopoietic stem cells through a tunable hydrolytically degradable thioester moiety. Moreover, the insights gained from understanding the native sickle bone marrow pathophysiology can be utilized to tailor the synthetic hydrogel system to address the complexities of the sickle marrow microenvironment. The success of this project will be a significant advancement in transplantation technology and provide a platform to support future stem cell-based therapies that benefit other underserved patient populations.