A novel device and rescue solution for the improved post-thaw viability and function of human stem cells used in cell therapy.

Cell Preservation Services, Inc., Owego NY

Investigators

Abstract

There are over 5000 human stem cell trials currently underway worldwide. Most of these trials use adipose-derived mesenchymal stem cells (adMSCs) while others use differentiated human embryonic stem cells (hESCs). While human induced pluripotent stem cells (iPSCs) are currently in limited trials in select countries, the future promise of these cells for treating disease worldwide is indisputable and their increasing use in the drug discovery/toxicity sciences is assured. Thus it is imperative to improve the bioprocessing and delivery of stem cells for patient use through developing new stem cell dedicated instruments, unique biomaterials, and improved methods of cell cryopreservation. Nearly half of stem cells are cryopreserved and thawed prior to infusion into the patient. Yet little attention has been paid to the post-thaw recovery, function and homing of these cells in patients that can be compromised as a consequence of preservation. CPSI Biotech personnel have worked in the stem cell therapy/cryopreservation arena for nearly 20 years and have reported that delayed onset cell death occurs up to several days post-thaw in all cell types including stem cells. Currently, many stem cell therapy companies thaw their cryopreserved cells immediately prior to infusion using a cryopreservation solution that is a component of their FDA issued IND. The most common method of thawing these cells is a standard (non-programmable) water bath and little to no emphasis is placed on delayed onset cell death that most assuredly occurs in the patient as a consequence of the thawing process that is exacerbated by the physical stress to the cells due to the infusion process. CPSI Biotech will address this issue by developing two new devices (StemThaw and StemTrans) and one unique recovery reagent (StemRevive). In Phase I CPSI?s prototype dry thaw system, SmartThaw, will be tested as a dedicated stem cell thawing device (StemThaw) that uses stem cell-specific thaw profiles that yield improved post-thaw outcome compared to standard methods. In addition, a post-thaw dilution reagent (StemRevive) will be developed that will reduce the delayed onset cell death known to occur 24 to 48 hours post- thaw. The combination of these two complementary technologies should improve the viability, function and engraftment of stem cells while at the same time limiting the chance of post- therapy rejection. Phase 2 will be dedicated to developing a unique device, StemTrans, that will be designed for the improved shipping and storage of cryopreserved and hypothermically stored stem cells. The Phase 1 Specific Aims are the following: 1) Define and develop unique cell type matched thawing programs for StemThaw that improve the post-thaw outcome of adMSCs, hESCs and iPSCs. 2) Define the optimal formulation of StemRevive as an additive reagent to thawed adMSCs, hESCs and iPSCs to prevent delayed onset cell death resulting in optimal viability. 3) Combine StemThaw and StemRevive together to determine efficacy. Phase 2 specific aims will include: (1) Develop and test unique thaw programs for StemThaw defined by Phase 1. (2) Develop StemTrans for the improved distribution of cryopreserved stem cells. (3) Determine if the optimal StemThaw and StemRevive combination defined in Phase 1 results in improved homing and engraftment in a mouse SCID model. (4) Test the combination of StemTrans, StemThaw and StemRevive as a candidate platform for the improved shipping, storing, thawing and recovery system that will yield improved viability, function and engraftment of stem cells for stem cell therapy thus limiting graft rejection and improving stem cell therapy efficacy.