Evaluation of the Spanish population coverage of a prospective HLA haplobank of induced pluripotent stem cells

Abstract

Background iPSC (induced pluripotent stem cells) banks of iPSC lines with homozygous HLA (human leukocyte antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population. Methods To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, HLA-B, and HLA-DRB1 with different stringencies: high resolution, low resolution, and beneficial mismatch. Results We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide HLA-A, HLA-B, and HLA-DRB1 matching for 28.23% of the population. Conclusion We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.

Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy

“…Development of an HLA homozygous iPSC bank in countries with high HLA variability may require more time and money to achieve wider coverage. For instance, 631 HLA homozygous iPSCs would be required to cover 90% of the Spanish population, while less than 200 iPSCs are required to reach the same coverage in Korea [ 111 ]. Reducing the required number of matching HLA alleles may help to reduce the number of iPSC lines required to cover most of the population in countries with high HLA variability.…”

Public Cord Blood Banks as a source of starting material for clinical grade HLA-homozygous induced pluripotent stem cells

“…The whole Spanish cord blood registry comprises 52,220 donations. From the 9419 which are genotyped in high resolution, we identified 109 homozygous units corresponding to 43 different haplotypes and we ranked the haplotypes priority according to the cumulative coverage capacity for HLA matching, as previously described [12]. The average pre-freeze content in CD34+ in the homozygous units was 5.51 × 10 6 .…”

“…This approach has shown promising results in primates [10]. Since HLA haplotypes differ in each geographical area, several studies have identified the most common haplotypes that would serve a national or regional population and calculated the number of HLA homozygous iPSC lines (haplolines) to cover a significant percentage [9,11,12]. Cord blood banks provide an excellent source of starting material for the production of iPSC: the samples are banked in great numbers, they are already HLA-typed and screened for the presence of virus and pathologies [13].…”

“…In this article, we report our experience to obtain CD34+ from homozygous donors to make iPSC haplolines following a procedure that complies with regulatory standards for ATMP starting materials and that can be adopted by other CBB with an interest in creating iPSC haplobanks. The process was performed within the Spanish haplobank project (IPS-PANIA) on nine CB units corresponding to HLA haplotypes estimated to provide the widest possible coverage of the Spanish population [12].…”

Somatic Reprogramming—Above and Beyond Pluripotency

“…These lines can be subject to regulatory clearance via vigorous tests on their genome stability, viral contamination, differentiation capability, and tumorigenicity [ 149 , 150 ]. Thus, the idea of haplobanking of HLA-homozygous iPSCs was spawned [ 152 , 153 , 154 ]. Notably, the first clinical trial led by Dr. Masayo Takahashi used autologous iPSC for treating neovascular age-related macular degeneration (AMD).…”