Optimisation and quality control of cell processing for autologous stem cell transplantation

Watts, Michael; Linch, David C.

doi:10.1111/bjh.14378

Cited by 35 publications

(25 citation statements)

References 83 publications

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“…Close monitoring is needed for optimization of safety and quality control, and prompt and reproducible engraftment is the best guide to graft potency [15]. A recent study of long-term storage of autologous grafts for >60 months or 12 through ≥60 months demonstrated no negative effect on hematopoietic recovery as compared with storage for ≤12 months [16].…”

Section: Discussionmentioning

confidence: 99%

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

Keever-Taylor

Heimfeld

Steinmiller

et al. 2017

Biology of Blood and Marrow Transplantation

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To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases–sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with “Critical Elements.” We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34+HPC) graft specifications included ≥70% viable CD34+ cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34+HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 106 viable CD34+ cells/kg (range, 3.9 to 12.8) for HALT-MS and 5.6 × 106 viable CD34+ cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34+ cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34+/kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34+ HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34+ cells. Manufacturing of Auto-CD34+HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets.

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Section: Discussionmentioning

confidence: 99%

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

Keever-Taylor

Heimfeld

Steinmiller

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Whereas proliferation may be a phenotype considered useful for evaluating the potency of autologous hematopoietic stem cells for bone marrow transplantation, interlaboratory reproducibility of commonly performed colony forming unit (CFU) assays is problematical [ 24 ]. Sample tests may poorly reflect the administered bulk clinical product and closely monitoring prompt engraftment after administration remains one of the most reliable indicators of quality [ 25 ]. For this and umbilical cord blood potency assessment [ 26 ], rapid functional assays are required.…”

Section: The Challenge Of Potency In Cell-based Therapeuticsmentioning

confidence: 99%

Advantages of Graphene Biosensors for Human Stem Cell Therapy Potency Assays

Amărandi

Becheru

Vlăsceanu

et al. 2018

BioMed Research International

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Regenerative medicine is challenged by the need to conform to rigorous guidelines for establishing safe and effective development and translation of stem cell-based therapies. Counteracting widespread concerns regarding unproven cell therapies, stringent cell-based assays seek not only to avoid harm but also to enhance quality and efficacy. Potency indicates that the cells are functionally fit for purpose before they are administered to the patient. It is a paramount quantitative critical quality attribute serving as a decisive release criterion. Given a broad range of stem cell types and therapeutic contexts the potency assay often comprises one of the most demanding hurdles for release of a cell therapy medicinal product. With need for improved biomarker assessment and expedited measurement, recent advances in graphene-based biosensors suggest that they are poised to be valuable platforms for accelerating potency assay development. Among several potential advantages, they offer versatility for sensitive measurement of a broad range of potential biomarker types, cell biocompatibility for direct measurement, and small sample sufficiency, plus ease of use and point-of-care applicability.

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“…Cryopreservation has a direct impact on the engraftment potential of stem cells from BM, peripheral blood (PB), and cord blood sources. Fast freeze rate is deleterious to clonogenic recovery and could be a major factor for engraftment failure 68, 69, 70. Thus, caution must be taken in designing rate-controlled freezer programs when using cryopreserved stem cell products.…”

Section: Main Textmentioning

confidence: 99%

Genetic Engineering and Manufacturing of Hematopoietic Stem Cells

Wang

Rivière

2017

Molecular Therapy - Methods & Clinical Development

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The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Reproducible manufacturing of high-quality, clinical-grade, genetically engineered HSCs is the foundation for broadening the application of this technology. Herein, the current state-of-the-art manufacturing platforms to genetically engineer HSCs as well as the challenges pertaining to production standardization and product characterization are addressed in the context of primary immunodeficiency diseases (PIDs) and other monogenic disorders.

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Optimisation and quality control of cell processing for autologous stem cell transplantation

Cited by 35 publications

References 83 publications

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

Advantages of Graphene Biosensors for Human Stem Cell Therapy Potency Assays

Genetic Engineering and Manufacturing of Hematopoietic Stem Cells

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