Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy
| العنوان: | Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy |
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| المؤلفون: | Ashley N. Bushdorf, Todd M. Brusko, Katherine S. Brown, Jeffrey A. Bluestone, Leeana D. Peters, Judit Cserny, Angela P. Lares, Howard R. Seay, Morey Kraus, Mark A. Atkinson, John R. Wingard, Kate Falcon Girard, Heather L. Brown, Amy L. Putnam, Kristi T. Balavage, Michael J. Haller, Emma Rosenau, Amanda L. Posgai |
| المصدر: | Molecular Therapy. Methods & Clinical Development Molecular Therapy: Methods & Clinical Development, Vol 4, Iss C, Pp 178-191 (2017) |
| بيانات النشر: | American Society of Gene & Cell Therapy, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Adoptive cell transfer, lcsh:QH426-470, Regulatory T cell, type 1 diabetes, medicine.medical_treatment, Stem Cell Research - Umbilical Cord Blood/ Placenta - Human, chemical and pharmacologic phenomena, Human leukocyte antigen, Hematopoietic stem cell transplantation, Umbilical cord, Autoimmune Disease, Vaccine Related, 03 medical and health sciences, 0302 clinical medicine, Stem Cell Research - Nonembryonic - Human, regulatory T cell, Genetics, Medicine, lcsh:QH573-671, Molecular Biology, adoptive cell transfer, Transplantation, 5.2 Cellular and gene therapies, lcsh:Cytology, business.industry, Prevention, Inflammatory and immune system, T-cell receptor, autoimmunity, FOXP3, hemic and immune systems, Stem Cell Research, 3. Good health, lcsh:Genetics, 030104 developmental biology, medicine.anatomical_structure, good manufacturing practices, Cord blood, Immunology, cord blood, Molecular Medicine, Immunization, Original Article, Development of treatments and therapeutic interventions, T cell receptor, business, 030215 immunology, Stem Cell Research - Umbilical Cord Blood/ Placenta |
| الوصف: | Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory Tcells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26× 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR). Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder Tcell proliferation. Immunosequencing of the Tcell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following invitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2329-0501 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23c244191afbb08a5a577c85554dc76bTest http://europepmc.org/articles/PMC5363324Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....23c244191afbb08a5a577c85554dc76b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23290501 |
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