In Utero Model to Assess the Fate of Transplanted Human Cells for Translational Research and Pediatric Therapies

In Utero Model to Assess the Fate of Transplanted Human Cells for Translational Research and Pediatric Therapies

Funding Type: 
Early Translational I
Grant Number: 
TR1-01269
Award Value: 
$3,143,398
Stem Cell Use: 
Embryonic Stem Cell
Status: 
Closed
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

Currently, the treatment for many childhood illnesses are complicated by the therapies necessary to ensure transplanted cells persist, are effective, and do not result in health complications. These studies focus on ways to provide treatments prenatally before birth safely and efficiently, and to address bottlenecks such as the expansion of cells that would be useful for transplantation. These include umbilical cord blood cells and more primitive precursors obtained from human embryonic stem cells. Our studies have shown effective methods for expanding these cell populations, and assessing their use for transplantation. Studies continue to explore the safety and efficiency of these novel therapies for fetuses diagnosed in utero with an inherited blood cell disorder.

Year 2

Currently, treatment for many childhood blood-related illnesses is complicated by the therapies necessary to ensure transplanted cells persist, are effective, and do not result in further complications that compromise health. These studies focus on ways to provide treatments before birth in a safe and efficient manner, and to address bottlenecks such as the expansion of cells prior to transplantation that would be needed to be curative, and methods to safely monitor the cells post-transplant in young individuals. Cells of interest include umbilical cord blood cells and more primitive hematopoietic precursors obtained from human embryonic stem cells. Our studies have shown effective methods for expanding these cell populations, collecting them in a clinically acceptable manner, and assessing their use for transplantation. Studies continue to explore the safety and efficiency of these novel therapies for fetuses diagnosed in utero with inherited blood cell disorders, and the use of in vivo imaging to monitor the cells safely post-transplantation.

Year 3

The current treatment for many childhood blood-related diseases is complicated by toxic regimens that are needed to ensure transplanted cells from donors persist and do not result in complications that can compromise health. These studies focus on new ways to safely transplant the necessary blood stem cells to treat these diseases prior to birth, and new techniques to monitor the fate of the cells post-transplantation. Outcomes of these studies have shown efficient methods to expand umbilical cord blood hematopoietic stem cells needed in the quantity required for efficient transplantation, safe and clinically relevant methods to transplant the cells prenatally, and effective methods to monitor the cells postnatally that confirm persistence and in the anatomical sites where they reside.

Year 4

These studies have two primary goals, to compare and contrast the fate of transplanted human cells from two immature cell sources (umbilical cord blood and human embryonic stem cell), and to use in vivo imaging to monitor the fate of the transplanted cells. Major findings during the reporting period include that expanded cord blood cells showed high levels of engraftment when monitored by imaging; no adverse events were detected; imaging was a good predictor of transplant tolerance and that the cells were not rejected; and that transplant of undifferentiated or differentiated human embryonic stem cells did not result in teratoma formation or adverse effects. Umbilical cord blood cells were found to be the most efficient using the paradigms tested.

© 2013 California Institute for Regenerative Medicine