Kidney and Metabolic Bone Diseases Vol.29 No.1(7)

Theme Cell biology of tooth
Title Collection of human leukocyte antigen-haplotype homo-dental pulp cells and application for regenerative medicine
Publish Date 2016/01
Author Ken-ichi Tezuka Department of Tissue and Organ Development, Gifu University Graduate School of Medicine
[ Summary ] Human dental pulp cells (DPCs) are present in the cell population isolated from dental pulp tissues. We reported that viral introduction of four transcription factors (OCT3/4, SOX2, KLF4, and c-MYC) can reprogram DPCs into induced pluripotent stem (iPS) cells, which closely resemble embryonic stem cells. However, we also found that establishing quality-controlled iPS cell lines from a large number of individual patients is not easy and their validation requires considerable time and expenditure. Human leukocyte antigen (HLA) plays an important role in the rejection of allogenic transplants of tissues and cells. Recently, tissue transplantation has been conducted without complete HLA matching because of shortage of donors. Instead of matching HLA types, immunosuppressants are frequently used to prevent hostto-graft and graft-to-host immune reactions ; however, when the immune system function is suppressed, there is increased susceptibility to infectious diseases and cancers. To solve this problem, usage of HLA haplotype-homo donors has been considered in iPS cell therapy. HLA haplotype-homo donors have two identical HLA gene sets, resulting in presentation of HLA molecules half in the variation. Therefore, iPS cells derived from HLA haplotype-homo donors are expected to be successfully transplanted in many patients with decreased possibility of rejection. We screened 107 DPC lines and identified two patients having only one genotype for each of three HLA loci, A, B, and DRB1. If iPS cells are established from these two patients, these cells are expected to show a complete match with approximately 20 % of the Japanese population.
We have also discussed the advantages and disadvantages of using DPCs as a somatic cell source for iPS cell banking and regenerative medicine in the future.
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