Measuring the Potency of a Stem Cell Therapeutic

Harper, Holli; Rich, Ivan N.

doi:10.1007/978-1-4939-1785-3_4

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…The potency of the RS is always 1. The potency ratios of both stem cell populations should be greater than 1 to provide assurance that the stem cells demonstrate sufficient engraftment potential when transplanted into the patient [37][38][39][40]. Abbreviations: CFC-GEMM, colony-forming cell-granulocyte, erythroid, macrophage, megakaryocyte; HPP-SP, high proliferative potential-stem and progenitor cell.…”

Section: Resultsmentioning

confidence: 99%

“…outcome (discussed in the Potency and Clinical Outcome section). It is obvious that misleading assumptions have been introduced that have led to misinterpretation of what potency is and how it should be measured [37][38][39][40].…”

Section: Minimum Testing Criteria and Their Limitationsmentioning

confidence: 99%

“…A further 6 samples (18.75%) show that one or both of the stem cell populations exhibit a potency ratio similar to or slightly higher than the reference standard. This might be interpreted as being adequate for transplantation; however, as explained previously, both stem cell quality and potency need to be taken into consideration to release the product for use [37][38][39][40]. This allows the assay to demonstrate an accuracy to predict engraftment of more than 90% [38,40].…”

Section: Measuring Stem Cell Stability and Confirmatory Potency Testimentioning

confidence: 99%

“…Proliferation potential is determined by the slope of the cell dose-response linear regression. The steeper the slope, the greater the proliferation potential, the more primitive the stem cell population, and the greater its potency and engraftment potential [37][38][39][40]. The results demonstrate not only that the TNC fraction masks and underestimates the functional capacity of the stem cells but also that the segment is not a good representative of the unit when based on the MNC fraction.…”

Section: Measuring Stem Cell Stability and Confirmatory Potency Testimentioning

confidence: 99%

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

Rich

2015

Stem Cells Translational Medicine

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Minimum Testing Criteria and Their Limitationsmentioning

confidence: 99%

Section: Measuring Stem Cell Stability and Confirmatory Potency Testimentioning

confidence: 99%

Section: Measuring Stem Cell Stability and Confirmatory Potency Testimentioning

confidence: 99%

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

Rich

2015

Stem Cells Translational Medicine

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Mitos y realidades del uso de las células troncales en la terapia oftalmológica

Gulías-Cañizo

Castro‐Muñozledo

2016

Revista Mexicana de Oftalmología

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Detecting primitive hematopoietic stem cells in total nucleated and mononuclear cell fractions from umbilical cord blood segments and units

et al. 2015

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BackgroundRare hematopoietic stem cell populations are responsible for the transplantation engraftment process. Umbilical cord blood (UCB) is usually processed to the total nucleated cell (TNC), but not to the mononuclear cell (MNC) fraction. TNC counts are used to determine UCB unit storage, release for transplantation and correlation with time to engraftment. However, the TNC fraction contains varying concentrations of red blood cells, granulocytes, platelets and other cells that dilute and mask the stem cells from being detected. This does not allow the quality and potency of the stem cells to be reliably measured.Methods63 UCB segments and 10 UCB units plus segments were analyzed for the response of both primitive lympho-hematopoietic and primitive hematopoietic stem cells in both the TNC and MNC fractions. The samples were analyzed using a highly sensitive, standardized and validated adenosine triphosphate (ATP) bioluminescence stem cell proliferation assay verified against the colony-forming unit (CFU) assay. Dye exclusion and metabolic viability were also determined.ResultsRegardless of whether the cells were derived from a segment or unit, the TNC fraction always produced a significantly lower and more variable stem cell response than that derived from the MNC fraction. Routine dye exclusion cell viability did not correspond with metabolic viability and stem cell response. Paired UCB segments produced highly variable results, and the UCB segment did not produce similar results to the unit.DiscussionThe TNC fraction underestimates the ability and capacity of the stem cells in both the UCB segment and unit and therefore provides an erroneous interpretation of the of the results. Dye exclusion viability can result in false positive values, when in fact the stem cells may be dead or incapable of proliferation. The difference in response between the segment and unit calls into question the ability to use the segment as a representative sample of the UCB unit. It is apparent that present UCB processing and testing methods are inadequate to properly determine the quality and potency of the unit for release and use in a patient.

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Measuring the Potency of a Stem Cell Therapeutic

Cited by 3 publications

References 7 publications

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

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

Mitos y realidades del uso de las células troncales en la terapia oftalmológica

Detecting primitive hematopoietic stem cells in total nucleated and mononuclear cell fractions from umbilical cord blood segments and units

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