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

Abstract

Background The increasing number of clinical trials for induced pluripotent stem cell (iPSC)-derived cell therapy products makes the production on clinical grade iPSC more and more relevant and necessary. Cord blood banks are an ideal source of young, HLA-typed and virus screened starting material to produce HLA-homozygous iPSC lines for wide immune-compatibility allogenic cell therapy approaches. The production of such clinical grade iPSC lines (haplolines) involves particular attention to all steps since donor informed consent, cell procurement and a GMP-compliant cell isolation process. Methods Homozygous cord blood units were identified and quality verified before recontacting donors for informed consent. CD34+ cells were purified from the mononuclear fraction isolated in a cell processor, by magnetic microbeads labelling and separation columns. Results We obtained a median recovery of 20.0% of the collected pre-freezing CD34+, with a final product median viability of 99.1% and median purity of 83.5% of the post-thawed purified CD34+ population. Conclusions Here we describe our own experience, from unit selection and donor reconsenting, in generating a CD34+ cell product as a starting material to produce HLA-homozygous iPSC following a cost-effective and clinical grade-compliant procedure. These CD34+ cells are the basis for the Spanish bank of haplolines envisioned to serve as a source of cell products for clinical research and therapy.

Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population

“…CB donors homozygous for the most frequent HLA-A, HLA-B and HLA-DRB1 haplotypes were chosen following an immunogenetic study to obtain the widest coverage of the Spanish population [ 19 ]. Homozygous CB samples had been identified in Spanish CB banks, and the selected CB units were quality verified; all participating donors signed a specific informed consent form for the use of the donated CB to generate hiPSC haplolines [ 20 ].…”

The fulfilled promise and unmet potential of umbilical cord blood

“…CBUs have been established as preferable source materials for creation of induced pluripotent stem cells (iPSC) [92] with HLA homozygous units considered as the ideal start for creation of iPSC for allogeneic cell therapies [93,94 ▪ ]. In the NK field, the ability of the iPSC platform to accommodate genetic manipulation and creation of large-scale cell banks, has received significant attention for the generation of off-the-shelve inventories of iPSC-derived modified NK cell therapy products displaying optimized potential for expansion and preservation after transplant, and targeted tumor cell killing potency [95].…”

“…In the NK field, the ability of the iPSC platform to accommodate genetic manipulation and creation of large-scale cell banks, has received significant attention for the generation of off-the-shelve inventories of iPSC-derived modified NK cell therapy products displaying optimized potential for expansion and preservation after transplant, and targeted tumor cell killing potency [95]. The advancement of the iPSC-derived cell therapy field has resulted in world-wide pursuit of cohorts of HLA homozygous CBUs providing high population coverages [93,96]. This is another example of how recent scientific advances in stem cell biology and cellular therapies have differentially shaped the (perceived) value of individual CBUs.…”

Generation of a bank of clinical-grade, HLA homozygous iPSC lines with high coverage of the Spanish population

“…19 Homozygous CB samples had been identi ed in Spanish CB banks and the selected CB units were quality veri ed; all participating donors signed a speci c Informed Consent for the use of the donated CB to generate hiPSC haplolines. 20…”