PMID- 38093328 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240125 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 14 IP - 1 DP - 2023 Dec 13 TI - Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population. PG - 366 LID - 10.1186/s13287-023-03576-1 [doi] LID - 366 AB - BACKGROUND: Induced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population. METHODS: The Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit. RESULTS: The iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms. CONCLUSIONS: Here, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP). CI - (c) 2023. The Author(s). FAU - Kuebler, B AU - Kuebler B AUID- ORCID: 0000-0002-4472-871X AD - Pluripotent Stem Cell Group, Regenerative Medicine Program, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. AD - Program for Translation of Regenerative Medicine in Catalonia (P-[CMRC]), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. FAU - Alvarez-Palomo, B AU - Alvarez-Palomo B AD - Advanced and Cell Therapy Service, Banc de Sang I Teixits, Edifici Dr. Frederic Duran I Jorda, Passeig de Taulat, 106-116, 08005, Barcelona, Spain. FAU - Aran, B AU - Aran B AD - Pluripotent Stem Cell Group, Regenerative Medicine Program, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. AD - Program for Translation of Regenerative Medicine in Catalonia (P-[CMRC]), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. FAU - Castano, J AU - Castano J AD - Advanced and Cell Therapy Service, Banc de Sang I Teixits, Edifici Dr. Frederic Duran I Jorda, Passeig de Taulat, 106-116, 08005, Barcelona, Spain. AD - Advanced Therapy Platform, Hospital Sant Joan de Deu de Barcelona, Pg. de Sant Joan de Deu, 2, Espluges de Llobregat, 08950, Barcelona, Spain. FAU - Rodriguez, L AU - Rodriguez L AD - Advanced and Cell Therapy Service, Banc de Sang I Teixits, Edifici Dr. Frederic Duran I Jorda, Passeig de Taulat, 106-116, 08005, Barcelona, Spain. FAU - Raya, A AU - Raya A AD - Program for Translation of Regenerative Medicine in Catalonia (P-[CMRC]), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. araya@idibell.cat. AD - Stem Cell Potency Group, Regenerative Medicine Program, Institut d Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. araya@idibell.cat. AD - Centre for Networked Biomedical Research On Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. araya@idibell.cat. AD - Institucio Catalana de Recerca I Estudis Avancats (ICREA), Barcelona, Spain. araya@idibell.cat. FAU - Querol Giner, S AU - Querol Giner S AD - Advanced and Cell Therapy Service, Banc de Sang I Teixits, Edifici Dr. Frederic Duran I Jorda, Passeig de Taulat, 106-116, 08005, Barcelona, Spain. squerol@bst.cat. AD - Transfusional Medicine Group, Vall d'Hebron Research Institute, Autonomous University of Barcelona (UAB), Barcelona, Spain. squerol@bst.cat. FAU - Veiga, A AU - Veiga A AD - Pluripotent Stem Cell Group, Regenerative Medicine Program, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. aveiga@idibell.cat. AD - Program for Translation of Regenerative Medicine in Catalonia (P-[CMRC]), Hospital Duran I Reynals, Gran Via de L'Hospitalet, 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain. aveiga@idibell.cat. LA - eng GR - Retos project iPS-PANIA/Ministerio de Ciencia e Innovacion/ GR - grant no. RTC-2017-6000-1/Ministerio de Ciencia e Innovacion/ GR - PID2021-123925OB-100/Ministerio de Ciencia e Innovacion/ GR - PT20/00171/Instituto de Salud Carlos III/ GR - 2021-SGR-00974/Agencia de Gestio d'Ajuts Universitaris i de Recerca/ PT - Journal Article DEP - 20231213 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-A Antigens) SB - IM MH - Humans MH - *Induced Pluripotent Stem Cells/metabolism MH - HLA-DRB1 Chains/metabolism MH - HLA Antigens/metabolism MH - HLA-B Antigens/metabolism MH - HLA-A Antigens/metabolism PMC - PMC10720139 OTO - NOTNLM OT - GMP manufacturing OT - HLA matching OT - Haplobank OT - Induced pluripotent stem cells OT - Regenerative medicine COIS- The authors declare that they have no competing interests. EDAT- 2023/12/14 06:42 MHDA- 2023/12/17 09:44 PMCR- 2023/12/13 CRDT- 2023/12/14 00:07 PHST- 2023/08/10 00:00 [received] PHST- 2023/11/16 00:00 [accepted] PHST- 2023/12/17 09:44 [medline] PHST- 2023/12/14 06:42 [pubmed] PHST- 2023/12/14 00:07 [entrez] PHST- 2023/12/13 00:00 [pmc-release] AID - 10.1186/s13287-023-03576-1 [pii] AID - 3576 [pii] AID - 10.1186/s13287-023-03576-1 [doi] PST - epublish SO - Stem Cell Res Ther. 2023 Dec 13;14(1):366. doi: 10.1186/s13287-023-03576-1.