Potency, Proliferation and Engraftment Potential of Stem Cell Therapeutics: The Relationship between Potency and Clinical Outcome for Hematopoietic Stem Cell Products

Rich, Ivan N.

doi:10.4172/2157-7013.s13-001

Cited by 11 publications

(7 citation statements)

References 51 publications

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“…CD34+ cells are also found in the circulation and can be differentiated into hematopoietic, endothelial, and nonhematopoietic lineages and can promote angiogenesis (48) and cardiac repair after injury (49,50). The frequency of CD34+ cells in the BM is used as an indicator of BM potency in the transplant field, and these cells (51)(52)(53) have been shown to repair the damage associated with CVD. Furthermore, CD34+ cell therapy has been associated with positive outcomes in patients with refractory angina, and the frequency of circulating CD34+ cells has been associated with a decreased risk of future cardiovascular events (54).…”

Section: Correlation Of Bm-cd34+ Cells With Patient Sexmentioning

confidence: 99%

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database

Haller

Gyöngyösi

Chacon‐Alberty³

et al. 2021

Front. Cardiovasc. Med.

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Background: Sex-based differences are under-studied in cardiovascular trials as women are commonly underrepresented in dual sex studies, even though major sex-based differences in epidemiology, pathophysiology, and outcomes of cardiovascular disease have been reported. We examined sex-based differences in patient characteristics, outcome, and BM-CD34+ frequency of the ACCRUE (Meta-Analysis of Cell-based CaRdiac studies) database involving patients with acute myocardial infarction (AMI) randomized to autologous cell-based or control treatment.Methods: We compared baseline characteristics and 1-year follow-up clinical data: composite major adverse cardiac and cerebrovascular events (primary endpoint), and changes in left ventricular ejection fraction (LVEF), end-diastolic (EDV), and end-systolic volumes (ESV) (secondary efficacy endpoint) in women and men (N = 1,252; 81.4% men). Secondary safety endpoints included freedom from hard clinical endpoints.Results: In cell-treated groups, women but not men had a lower frequency of stroke, AMI, and mortality than controls. The frequency of BM-CD34+ cells was significantly correlated with baseline EDV and ESV and negatively correlated with baseline LVEF in both sexes; a left shift in regression curve in women indicated a smaller EDV and ESV was associated with higher BM-CD34+ cells in women.Conclusions: Sex differences were found in baseline cardiovascular risk factors and cardiac function and in outcome responses to cell therapy.

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Section: Correlation Of Bm-cd34+ Cells With Patient Sexmentioning

confidence: 99%

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database

Haller

Gyöngyösi

Chacon‐Alberty³

et al. 2021

Front. Cardiovasc. Med.

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“…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 [37–40]. This allows the assay to demonstrate an accuracy to predict engraftment of more than 90% [38, 40]. It is possible that the samples tested in this study were of low quality and/or potency prior to or after initial processing.…”

Section: New Perspectivesmentioning

confidence: 99%

“…After acknowledging the problems with current UCB testing, a call for next‐generation assays to measure potency was published in 2011 [34]. Since that time, the field has neither developed its own new or novel assays nor pursued or embraced assays that were already available [37, 38]. Nonetheless, one of the priorities of the newly formed Cord Blood Association is the “advancement and rapid adoption of new technology” [54].…”

Section: New Perspectivesmentioning

confidence: 99%

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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“…Consequently, most laboratories use the colony-forming unit assay to assess CBU potency. The CFU assay is a reliable indicator of hematopoietic stem cells proliferation and differentiation, and a good predictor of engraftment [5][6][7]. The principal drawbacks of the CFU assay are its known interlaboratory variability [8,9], the labor intensive nature of the assay and the 7 to 14 days of cellular growth required before getting the results, therefore delaying the release of a unit.…”

Section: Introductionmentioning

confidence: 99%

Validation of a rapid potency assay for cord blood stem cells using phospho flow cytometry: the IL-3-pSTAT5 assay

Simard

Fournier

Trépanier

2022

Preprint

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Public cord blood banks (CBBs) are required to measure cord blood units (CBUs) potency before their release, allowing for the identification of units that may be unsuitable for hematopoietic transplantation. We have developed a rapid flow cytometry assay based on the measurement of STAT-5 phosphorylation of CD34+ stem cells in response to IL-3 stimulation: the IL-3-pSTAT5 assay. To adapt the assay from a research setting to its implementation within our CBB regulated operations, we proceeded with a full method validation and a correlation comparison of the IL-3-pSTAT5 assay results with the colony-forming unit assay (CFU) results. A total of 60 CBUs cryopreserved in vials were analyzed by flow cytometry to determine the sensitivity, specificity, intra-assay precision, robustness, reproducibility and inter-laboratory agreement of the assay. The CFU assay was also done on the same samples for comparison purposes. The assay threshold was established at 50% CD34+CD45+pSTAT5+, which provides a 100% sensitivity and a 98.3% specificity. An average intra-assay CV of 7.3% was determined. All results met our qualitative results acceptance criteria regarding the inter-user and inter-laboratory agreements, IL-3 stimulation time, post-thaw incubation delay and staining time. The IL-3-pSTAT5 assay results correlated well with the total CFU determined using the CFU assay (r squared = 0.82, n = 56). This study shows that our rapid flow cytometry assay can be successfully validated and that the potency data obtained display good sensitivity, specificity and robustness. These results demonstrate the feasibility of implementing this assay within CBB operations, as a validated CB potency assay.

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Potency, Proliferation and Engraftment Potential of Stem Cell Therapeutics: The Relationship between Potency and Clinical Outcome for Hematopoietic Stem Cell Products

Cited by 11 publications

References 51 publications

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database

Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database

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

Validation of a rapid potency assay for cord blood stem cells using phospho flow cytometry: the IL-3-pSTAT5 assay

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