腎と骨代謝 Vol.29 No.1(7)


特集名 歯の細胞生物学
題名 HLAハプロタイプホモ歯髄細胞の収集と再生医療への応用
発刊年月 2016年 01月
著者 手塚 建一 岐阜大学大学院医学系研究科組織・器官形成
【 要旨 】 われわれは,医療廃棄物として大量に入手できる親知らずから細胞を取り出し,約100ラインからなる研究用ヒト歯髄細胞コレクションを構築した.その白血球型(human leukocyte antigen;HLA)を解析したところ,HLAハプロタイプホモという他家移植に有利な細胞を得ることができた.HLAは,他人の臓器や細胞を拒絶する反応に深く関わっている.多型に富み,他人同士でHLA型が完全に一致することはまれで,HLA型の「違い」が免疫系による拒絶反応やGVHDを惹起する.HLAハプロタイプホモのHLA型は,父母から同じハプロタイプのHLA遺伝子を受け継いだときに生じ,提示されるHLA分子の種類が半分になる.それゆえ,HLAをドナーからレシピエント方向に一致させやすい.とくに日本人は他の人種に比べてHLAハプロタイプに偏りがあり,HLA ハプロタイプホモドナーを見つけやすく,かつ,同じHLAハプロタイプホモ細胞で多くの患者をカバーできる特徴がある.そして,あらかじめ大量の細胞を用意しておくことで,脊髄損傷など緊急性を要する疾患にも,安全に他家移植による再生医療が行えるようになる.
Theme Cell biology of tooth
Title Collection of human leukocyte antigen-haplotype homo-dental pulp cells and application for regenerative medicine
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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