論文

静脈内投与安全性

Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.
Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, Kim YJ, Jo JY, Yoon EJ, Choi HJ, Kwon E.
Stem Cells Dev. 2011 Aug ; 20(8) : 1297-308. Epub 2011 Mar 17. PMID : 21303266
使用細胞:ヒト脂肪由来幹細胞
使用動物:ヌードマウス
被験者:脊髄損傷の患者8名

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変形性関節症

Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof-of-concept clinical trial.
Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS.
Stem Cells. 2014 May ; 32(5) : 1254-66. do i: 10.1002/stem. 1634. [Epub ahead of print] PMID : 24449146
被験者:変形性膝関節症の患者18名
研究デザイン:第1相、第2相臨床試験

Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients.
Fereydoun DAVATCHI, Bahar SADEGHI ABDOLLAHI, Mandana MOHYEDDIN, Farhad SHAHRAM, Behrooz NIKBIN
Int J Rheum Dis. 2011 May;14(2):211-5. doi: 10.1111/j.1756-185X.2011.01599.x. Epub 2011 Mar 4. PMID: 21518322
被験者:変形性膝関節症の患者4名
研究デザイン:臨床試験(対照群なし)

Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis.
Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, Farjad R, et al.
Arch Iran Med. 2012; 15(7): 422 – 428.
被験者:変形性膝関節症の患者6名
研究デザイン:臨床試験(対照群なし)

Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis.
Yong-Gon Koh, Yun-Jin Choi
Knee. 2012 Dec;19(6):902-7. doi: 10.1016/j.knee.2012.04.001. Epub 2012 May 14. PMID: 22583627
被験者:変形性膝関節症の患者25名
研究デザイン:臨床試験(対照群あり)

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重症下肢虚血疾患

Safety and effect of adipose tissue-derived stem cell implantation patients with clinical limb ischemia.
Han Cheol Lee, Sung Gyu An, Hye Won Lee, Jin-Sup Park, Kwang Soo Cha, et al.
Circulation journal, 76, 1750-1760, 2012.
被験者:バージャー病患者12名及び糖尿病性潰瘍患者3名
投与部位:症状の見られる四肢の筋肉

Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis.
Kazuhisa Kondo, Satoshi Shintani, Rei Shibata, Hisashi Murakami, Ryuichiro Murakami, Masayasu Imaizumi, Yasuo Kitagawa, Toyoaki Murohara
Arterioscler Tromb Vasc Biol., 2009;29:61-66, 2008.
使用細胞:マウス脂肪由来幹細胞
使用動物:マウス

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自己免疫疾患

Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells
Jeong Chan Ra, Sung Keun Kang, Il Seob Shin, Hyeong Geun Park, Sang Aun Joo, Jeong Geun Kim, Byeong-Cheol Kang, Yong Soon Lee4, Ken Nakama5, Min Piao, Bertram Sohl, Andras Kurtz
Journal of Translational Medicine 2011, 9:181
被験者:10名の自己免疫疾患患(自己免疫性内耳障害1名、多発性硬化症1名、多発性筋炎1名、アトピー性皮膚炎4名、リュウマチ3名)
10名の自己免疫疾患患者に対して、患者自身から採取した脂肪から脂肪由来幹細胞を分離し、培養を行って自己脂肪由来幹細胞を調製し、静脈投与した。経過観察を行った結果、全ての症例で重大な有害事象は報告されず、症状の改善が認められた。

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus
Lingyun Sun, Dandan Wang, Jun Liang, Huayong Zhang, Xuebing Feng, Hong Wang et. al.
Arthritis Rheum, Aug; 62(8): 2467-75, 2010.
被験者:全身性エリテマトーデスの患者16名

Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study
Peter Connick, Madhan Kolappan, Charles Crawley, Daniel J Webber, Rickie Patani, et. al.
Lancet Neurol, Jan9, 2012
被験者:多発性硬化症の患者10名

Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation
Eun Wha Choi, Il Seob Shin,2 So Young Park, Ji Hyun Park, Jong Sung Kim, et. al.
ARTHRITIS & RHEUMATISM, Vol. 64, No. 1, January 2012, pp 243–253
実験動物:マウス

The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice
Yixuan Zhou, Jingdong Yuan, Bin Zhou, Austin J. Lee, Albert J. Lee, Maher Ghawji Jr, et. al.
Immunology, 133, 133-140, 2011
実験動物:マウス

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顔面再建・皮膚再生治療

Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (parry-romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera
Kyung Suk Koh, Tae Suk Oh, Hoon Kim, In Wook Chung, Kang Woo Lee, et. al.
Transplantation surgery and research, Volume 69, Number 3, 331-337, 2012
被験者:10名のロンバーグ病患者(男性5人、女性5人、平均年齢28歳)

Antiaging treatment of the facial skin by fat graft and adipose-derived stem cells
Luiz Charles-de-Sa et al.
Plastic and Reconstructive Surgery, Volume 135, Number 4, 2015.
被験者:美容治療を希望する6名の被験者(男性1名、女性5名)

Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells
Kotarao Yoshimura et al.
Dermatol Surg, 34:1178-1185, 2008
被験者:顔面脂肪萎縮症の患者6名(深在性エリテマトーデス5名、ロンバーグ病1名)

Cell-assisted lipotransfer for the treatment of Parry-Romberg Syndrome
Yanko Castro-Govea et al.
Archives of plastic surgery, 39:659-662,2012
1名のロンバーグ病患者(35歳男性)に対してCALにより脂肪移植を行った結果、ロンバーグ病の症状の改善が認められた。(症例報告)

Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging
Byung-Soon Park et al.
Dermatol Surg, 34:1323-1326,2008
Pilot studyとして、1名の光老化の患者に脂肪から分離した脂肪由来幹細胞(purified autologous processed lipoaspirate)を顔面に投与した。重大な有害事象は認められず、投与後2カ月後の肉眼観察の結果、明らかなしわの改善効果が確認された。

Anti-wrinkle effects of adipose tissue-derived mesenchymal stem cells in a UV-irradiated hairless mouse model
Bae-Hwan Kim et al.
Tissue engineering and regenerative medicine, Vol. 7, No.5, 583-591, 2010
実験動物:Hairless Mouse

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アルツハイマー病治療

The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer's disease mice.

Kim, Saeromi, et al.,PloS one 7.9 (2012): e45757.

細胞由来:脂肪由来間葉系幹細胞 投与対象:マウス
投与方法:静脈内投与 投与細胞数:1.0x106 cells、13回の反復投与

Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer’s disease mice.

Yan, Yufang, et al., Neural regeneration research 9.8 (2014): 798.

細胞由来:ヒト脂肪由来間葉系幹細胞 投与対象:マウス
投与方法:静脈投与

Intracerebral Transplantation of Adipose-Derived Mesenchymal Stem Cells Alternatively Activates Microglia and Ameliorates Neuropathological Deficits in Alzheimer’s Disease Mice.

Ma, Tuo, et al., Cell transplantation 22.1_suppl (2013): 113-126.

細胞由来:ヒト脂肪由来間葉系幹細胞 投与対象:マウス
投与方法:静脈内投与 投与細胞数:1.0x106 cells、13回の反復投与

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アトピー性皮膚炎

Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.

(Ra, Jeong Chan, et al.,Stem cells and development 20.8 (2011): 1297-1308.)-「Rbio資料」

細胞由来:自家脂肪由来間葉系幹細胞 投与対象:マウス/ヒト
投与方法:静脈内投与(細胞数:マウス2.5×108 cells/kg、ヒト4.0×108 cells)

Effect of the multiple intravenous administration of cultured human autologous adipose-derived stem cells on tumor biomarker levels.

(Ra, Jeong Chan, et al., J Clin Case Rep 2017, Vol 7(11): 1040) -「Rbio資料」

細胞由来:ヒト脂肪由来間葉系幹細胞 投与対象:ヒト
投与方法:静脈内投与(細胞数:1×108cells以上)

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関節リウマチ

Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells.

(Jeong Chan Ra et al.,Journal of translational Medicine, 9:181, 2011)

細胞由来:自家脂肪由来間葉系幹細胞(Biostar社から培養した細胞)
投与対象:ヒト(自己免疫疾患患者)
投与方法:静脈投与

Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial.

(Jose M Alvaro-Gracia et al., Annals of the rheumatic diseases, Volume 76, Issue 1, 2017)

細胞由来:他家脂肪間葉系幹細胞
投与対象:ヒト(関節リウマチ患者)
投与デザイン
    試験群A:1.0X106cells/kg
    試験群B:2.0X106cells/kg
    試験群C:4.0X106cells/kg
    プラシーボ群
投与方法:静脈投与(3回投与)

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