Improving Quality and Potency Testing for Umbilical Cord Blood: A New Perspective

Abstract

SUMMARYThis article critically reviews current methods to test and characterize umbilical cord blood (UCB) for hematopoietic stem cell transplantation. These tests include total nucleated cell (TNC) count, viability, viable CD34-positive content, and the colony-forming unit assay. It is assumed that the data obtained are sufficient to perform a UCB stem cell transplant without actually determining the quality and potency of the stem cells responsible for engraftment. This assumption has led not only to a high graft failure rate attributed to low or lack of potency, but also to noncompliance with present statutes that require UCB stem cells to be of high quality and, indeed, potency for a transplant to be successful. New evidence now calls into question the quality of the data, based on the UCB processed TNC fraction because using this impure fraction masks and significantly underestimates the functionality of the stem cells in both the segment and the unit. It is proposed that UCB units should be processed to the mononuclear cell fraction and that new cost-effective technology that measures the quality and potency of UCB stem cells be implemented to achieve better practices in UCB testing. These changes would provide the transplant physician with the assurance that the stem cells will perform as intended and would reduce risk and increase safety and efficacy for the patient. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:967-973 SIGNIFICANCECurrent stem cell transplantation of umbilical cord blood cells requires testing that includes four basic parameters that do not determine whether the stem cells are of high quality, as required by the Stem Cell Therapeutic and Research Act of 2005. No cord blood units collected or transplanted so far have been tested for stem cell quality or potency. New scientific evidence calls into question cord blood processing and testing practices required by regulatory agencies and standards organizations. A new perspective is described that includes stem cell quality and potency testing that could reduce graft failure rates.

Noninvasive white blood cell quantification in umbilical cord blood collection bags with quantitative oblique back‐illumination microscopy

“…The high cost of CBUs is due, in part, to high discard rates of CBUs before cryopreservation. 2,9 Indeed, 66% to 75% of collected CBUs fail to meet storage criteria 10,11 due to insufficient volumes, 12 delayed arrival at the processing site, and, more importantly, low total nucleated cell counts, 13,14 which correlate with poor success rates of transplant engraftment. 15 Thus, there is an unmet need to monitor the contents of CBUs at the collection site (i.e., maternity unit) and assess the units' suitability for storage before undergoing further expensive processing at the CBB.…”

“…Despite the aforementioned advantages, the cost of procuring CBUs is over 10 times more than peripheral blood and bone marrow, which makes it less accessible to the end user and is causing a decrease in the use of UCB for transplantation. The high cost of CBUs is due, in part, to high discard rates of CBUs before cryopreservation . Indeed, 66% to 75% of collected CBUs fail to meet storage criteria due to insufficient volumes, delayed arrival at the processing site, and, more importantly, low total nucleated cell counts, which correlate with poor success rates of transplant engraftment …”

Quality and exploitation of umbilical cord blood for cell therapy: Are we beyond our capabilities?

“…Further improvements are also necessary to avoid negative effects on UCB viability (and function) by extended processing and storage times. This point is especially critical to guarantee UCB‐derived cell quality and to subsequently increase clinical outcomes (Spellman et al, ; Rich, ). Notably, improved strategies on this issue would also provide numerous advantages for banking systems, including rationalization of storage and considerable reduction in the costs associated with processing and banking of no viable UCB units.…”

Increased Expression of BIRC2, BIRC3, and BIRC5 from the IAP Family in Mesenchymal Stem Cells of the Umbilical Cord Wharton’s Jelly (WJSC) in Younger Women Giving Birth Naturally

“…The influence of various factors on the umbilical cord blood quality has been repeatedly studied [7][8][9][10][11][12][13][14][15][16][17][18]. However, there are very few studies on the influence of factors related to childbirth on the quality and potential of mesenchymal cells derived from the umbilical cord Wharton's jelly.…”