ミューズ細胞 ミューズ細胞の概要

ミューズ細胞

出典: フリー百科事典『ウィキペディア(Wikipedia)』 (2024/03/10 15:17 UTC 版)

特徴

  • ストレス耐性を有する[22]
  • 腫瘍性を持たない。他の幹細胞よりも短い時間でDNA損傷の修復が行われる[23]
  • 多能性幹細胞のマーカーの一つとして知られているStage-specific embryonic antigen (SSEA)-3陽性細胞として単離することが可能である[1][3][4][5]
  • 臍帯を含めた多様な臓器の結合組織、骨髄、末梢血中に存在する。骨髄移植で移植される細胞群のうちの~0.03%、骨髄、脂肪などから採取可能な間葉系細胞の数%に相当する[1]
  • 自己複製能と3胚葉由来の多種多様な細胞への分化能を有する多能性幹細胞である[1]
  • テロメラーゼ活性は体細胞と同程度で低く、腫瘍性を示さない[1][9][24]
  • 正常ヒト生体組織より遺伝子の導入などの人為的操作なしに多能性幹細胞として単離することが可能である。
  • 免疫抑制/調節効果、線維化抑制効果、血管新生効果、組織保護効果を示す[24]
  • sphingosine-1-phosphats (S1P)-S1P receptor 2のシステムにより、静脈経由または局所投与後、生体の損傷部位へと選択的に集積・生着する[25][26][27][28]
  • 傷害組織に生着後、組織に応じた細胞へと自発的に分化することで機能的な細胞を補充し組織を修復する。サイトカインや遺伝子導入による分化誘導を必要としない[1][25][26][27]
  • ドナー由来(他家)Muse細胞は特異な免疫特権があるため、HLA適合検査や長期の免疫抑制剤投与を必要とせず、直接投与可能である[28]
  • 従ってミューズ細胞を分離し、遺伝子操作などせず、ドナー細胞をそのまま点滴投与することによって様々な組織を修復させることができる。現在行われている治験はすべてHLA適合検査や免疫抑制剤投与をせずに直接ドナーミューズ細胞を点滴投与するものである。[29]

マーカー

ミューズ細胞は未分化ヒトES細胞などの多能性幹細胞のマーカーとして知られているSSEA-3を発現している細胞として同定された[1][30]。抗SSEA-3抗体を使用して単離したミューズ細胞のサイズはおよそ直径13-15μmである。ミューズ細胞はCD34 (造血幹細胞、脂肪幹細胞、VSELsのマーカー)やCD117 (造血幹細胞のマーカー)、Snai1・Slug (共に皮膚前駆細胞のマーカー), CD271・Sox10 (共に神経堤由来幹細胞のマーカー)、NG2・CD146 (共に血管周囲細胞のマーカー)、CD31・von Willebrand factor (共に血管内皮前駆細胞のマーカー)をすべて発現していないことから、これまでに報告のあったどの幹細胞とも異なる幹細胞である[1][31]

ミューズ細胞の分化能

In vitro

ミューズ細胞は培養系において、以下のようなマーカー陽性の細胞に自発的、またはサイトカインによる誘導で分化することが報告されている。

  1. 外胚葉系細胞 (nestin, NeuroD, Musashi, neurofilament, MAP-2, tyrosinase, MITF, gf100, TRP-1, DCT)[3][32]
  2. 中胚葉系細胞 (brachyury, Nkx2-5, smooth muscle actin, osteocalcin, oil red-(+) lipid droplets, desmin, WT-1, EYA1, Podocin, Megsin, Troponin-1, Cx43, Tbx20, ANP, Mlc1a, Mlc1v, CD31, CD34, Foxc1, Klf2)[1][3][33][34]
  3. 内胚葉系細胞 (GATA-6, α-fetoprotein, cytokeratin-7, cytokeratin-19, cytokeratin-18, albumin, DLK, CXCR4, c-Met, HepPar1, anti-Trypsin, OV6, Lyve1)[1][3][25][35]
  4. 傷害細胞・死細胞を貪食し、取り込んだ分化に必要なシグナル(転写因子等)を再利用することで、傷害細胞・死細胞と同じタイプの細胞に日単位で迅速分化する。ミューズ細胞は多能性を示すため、臓器内の複数の細胞種に分化できる[36]

In vivo

ヒトミューズ細胞が血中へ注入されるとS1Pに従って傷害部位に遊走し、傷害組織に入ると傷害細胞・死細胞を貪食し、取り込んだ分化シグナルを再利用して同一細胞に分化をすることで組織修復する[36]ことが以下の損傷モデル動物で確認されている。

  1. 心筋梗塞モデル[37]
  2. 脳梗塞モデル[26][38][39]
  3. 脳出血モデル[40]
  4. 腎不全モデル[33]
  5. 肝不全モデル[35]
  6. 肝部分切除モデル[25]
  7. 糖尿病性皮膚潰瘍モデル[27]
  8. 大動脈瘤[41]
  9. 筋変性モデル[1]
  10. 皮膚損傷モデル[1]
  11. 表皮水疱症モデル[42]
  12. 筋萎縮性側索硬化症モデル[43]
  13. 新生児低酸素性虚血性脳症モデル[44]
  14. 病原性大腸菌による急性脳症モデル[45]

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