. The long term objective of this investigation is to develop methods of post-thaw assessment that permit transplant sites to assess umbilical cord blood units (UCB) prior to transplant and can be used by UCB banks as a part of their quality control program. UCB is an important source of hematopoietic stem cells (HSCs) used in the treatment of a variety of diseases including blood cancer. UCB now comprises 28% of all HSC transplants performed in the USA every year, with 14,000 transplants to date performed in humans worldwide. The advantages of UCB are numerous: it can be collected at no risk to the donor;immediate availability in a bank;wider availability of diverse HLA genotypes with approximately 350,000 units banked;lower immune reactivity and lower inherent pathogen transmission. All indications are that the clinical applications for UCB will continue to grow. The vast majority of UCB units are collected and cryopreserved for later use. Considerable effort has been invested to improve the quality of UCB units by standardizing collection, processing and preservation. In spite of the aforementioned efforts in standardizing UCB processing, there have been reports of poor post thaw recovery of UCB units. There is not yet a standard metric or measure by which to quantify post-thaw potency of UCB products. Transplant studies of UCB suggest that both CD34+ and colony forming unit (CFU) content correlate with engraftment and long- term survival. Both of these assays are candidates for assessing post-thaw function. Hematopoietic cell products exhibit significant cell losses resulting from post-thaw apoptosis. More recent studies demonstrated that cells expressing early signs of apoptosis did not engraft in an animal transplant model suggesting significant functional impairment of the cells. Therefore, characterizing post-thaw apoptosis may be a clinically relevant post-thaw quality metric for UCB. Post thaw apoptosis may also be a marker for aging of the cells during storage. It is our hypothesis that post-thaw apoptosis measures can be a clinically relevant metric for damage during the preservation process and storage of UCB units.

Public Health Relevance

Umbilical cord blood units are used to treat a variety of diseases including blood cancer. This project develops assays that permit a doctor to determine if the unit is of sufficient quality that it can be used for therapeutic purposes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL112653-02
Application #
8457137
Study Section
Special Emphasis Panel (ZHL1-CSR-P (F2))
Program Officer
Wagner, Elizabeth
Project Start
2012-04-15
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$108,528
Indirect Cost
$37,128
Name
University of Minnesota Twin Cities
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455