Influence of aging on the quantity and quality of human cardiac stem cells

加齢がヒト心筋幹細胞の量と質に与える影響 (＜ミニ・レビュー＞中村賞受賞者)

Influence of aging on the quantity and quality of human cardiac stem cells

Creators Nakamura Tamami

加齢は様々な組織幹細胞の細胞老化を引き起こし,再生能を低下させることが知られている.そこでわれわれは,2歳から83歳までの心臓手術患者26名から得られたヒト心筋幹細胞を用いて,加齢がヒト心筋幹細胞の量と質に与える影響を検討した.まず心臓手術時に採取した右房組織の一部から,心筋幹細胞の一種であるCardiosphere-derived cell(CDC)を分離･培養した.そしてCDCの細胞老化とDNA障害の程度,および細胞機能(増殖能,成長因子発現量,血管新生能)について検討した.まず増殖能は年齢との間に明らかな関連はなく,全ての検体から実験に必要な十分量のCDCが培養可能であった.細胞老化のマーカーであるsenescence-associated β-galactosidase染色陽性率と,DNA障害のマーカーであるγH2AX陽性率については,65歳以上の患者由来CDCで高い傾向がみられた.しかし,心筋再生の主要なメカニズムであるパラクライン効果を担うVEGF,HGF,IGF-1,SDF-1,TGF-βの発現量は各検体で様々であり,加齢に伴う減少はみられなかった.In vitro血管新生アッセイにおいても,加齢による血管新生能低下はみられなかった.以上から,加齢がヒト心筋幹細胞の量と質に与える影響は,非常に限定的であることが明らかとなった.これは将来自家心筋幹細胞移植を臨床応用する際に,高齢心不全患者でも移植治療の適応となりうることを示す重要な結果である.

Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages(from 2 to 83 years old).We collected fresh right atria and cultured cardiosphere-derived cells(CDCs),which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated β-galactosidase and the DNA damage marker, γH2AX, showed a slightly higher trend in CDCs from older patients(≥65 years).The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-β varied among samples, and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients.

[ISSN]0513-1731

[NCID]AN00243156