パーキンソン病に対するCograftを用いた移植療法—ドナー側の年齢要因について—

Cografting Technique for the Treatment of Parkinson's Disease

I．はじめに

　副腎髄質クロマフィン細胞は一側黒質線条体ドーパミン系を破壊しておいたラットの線条体内に移植されると，apomorphineによる回転運動を減少させる^11）．また，1—methyl−4—phenyl−1, 2, 3, 6—tetrahydropyri—dine（MPTP）を用いて作成したマウスパーキンソン病モデルに副腎髄質を移植すると，宿主の内因性ドーパミン系の回復が促進される^3）．筆者らはこれまで，同モデルを用い，宿主に老齢マウスを用いた場合は内因性ドーパミン系の回復程度が若年マウスに比べて低いこと^5），ドナーに老齢マウスの副腎髄質を用いた場合は若年マウスに比べて，クロマフィン細胞の生着率が低いこと^9）を報告してきた．さらに，nerve growth factor（NGF）の源である末梢神経^{14, 22）}を副腎髄質とcograftするとドナーが若年マウスの場合，クロマフィン細胞の生着率が著明に向上する^10）．しかし，パーキンソン病が高齢者に好発する神経変性疾患であることを考えると，ドナーに老齢マウスを用いた検討も必要である．

Abstract

Intracerebral grafting of dopamine containing adrenal chromaffin cells to the brain of experimental animals can ameliorate the symptoms of experimentally induced Parkinson's disease. Clinical trials of adrenal autograft to the patients with Parkinson's disease are on-going with variable results and autopsy cases show poor sur-vivability of grafted chromaffin cells. The present study was performed to determine if transected peripheral nerve could provide sufficient nerve growth factor to enhance the survivability of grafted chromaffin cells. Survivability of grafted chromaffin cells increased when cografts with sciatic nerve were performed, and host dopaminergic fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. Although this enhanced survivability and recov-ery of host fibers were seen in cografted mice from ag-ing donors, the degree of these effects was greater in cografted mice from young donors. Considering these results, we suggest that methods to increase the survi-vability of grafted chromaffin cells be explored more deeply because such survivability might be closely re-lated to the functional recovery of patients with Parkin-son's disease, using this grafting procedure.