Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy

Sakai, Yoshio; Fukunishi, Shinya; Takamura, Masayuki; Kawaguchi, Kazunori; Inoue, Oto; Usui, Soichiro; Takashima, Shinya; Seki, Akihiro; Asai, Akira; Tsuchimoto, Yusuke; Nasti, Alessandro; Ho, Tuyen Thuy Bich; Imai, Yasuhito; Yoshimura, Kenichi; Murayama, Toshinori; Yamashita, Taro; Arai, Kuniaki; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Wada, Takashi; Harada, Kenichi; Higuchi, Kazuhide; Kaneko, Shuichi

doi:10.1016/j.reth.2021.04.003

Cited by 17 publications

(9 citation statements)

References 28 publications

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“…Recently, a multi-institutional clinical trial using freshly isolated autologous adipose tissue-derived regenerative cells was performed in Japan to treat seven NAFLD patients. 58 The results illustrated the improvement in the serum albumin level of six patients and prothrombin activity of five patients, and no treatment-related adverse events or severe adverse events were observed. This study illustrates the therapeutic potential of stem cell-based therapy in the treatment of NAFLD.…”

Section: Stem Cell-based Therapy: An Overview Of Current Clinical App...mentioning

confidence: 72%

Stem cell-based therapy for human diseases

Hoang

Pham

Bach

et al. 2022

Sig Transduct Target Ther

405

138

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Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

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Section: Stem Cell-based Therapy: An Overview Of Current Clinical App...mentioning

confidence: 72%

Stem cell-based therapy for human diseases

Hoang

Pham

Bach

et al. 2022

Sig Transduct Target Ther

405

138

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“…In the current study, we like to assess if curcumin preconditioning of MSCs can maintain this ameliorative effect and protect against return of the fibrosis which actually represent a critical challenge in use MSCs in therapy and still there is a controversy about the long term efficacy of stem cells, there many preclinical and clinical studies prove the reduction of liver fibrosis by MSCs injection [24][25][26] but maintaining its effect were achieved after many times of cell injection up to 9 injections in one experiment [27] and partially achieved in another studies [28][29] and not achieved at all in others [30][31]. So, we investigated the fibrosis degree on 12 th week and 24 th week of cell infusion and we found that no significant difference compared to that at 4 th week in cur + /nanoscaffold and this indicates that curcumin preconditioning of MSCs maintained the ameliorative effect of the primed MSCs and protected against the return of fibrosis compared to cur -/nanoscaffold which showed a return of fibrosis from 6.5% to 10.4% .…”

Section: Discussionmentioning

confidence: 99%

Curcumin Nanofiber PCL/PLGA/Collagen Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cells against Liver Fibrosis in Animal Model and Prevented its Recurrence

Tawfeek¹,

Kasem²,

Elshoala³

2023

Nanotheranostics

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The aim of this study is preconditioning of hBM-MSCs using curcumin modified nanomembrane to optimize therapy of hepatic fibrosis and preventing its recurrence. Methods: The nanomembrane was prepared by electrospinning technique and characterized using conventional method (cur - nanoscaffold and cur + nanoscaffold). Kinetic release of curcumin was also measured by spectrophotometry. MSCs were isolated from human bone marrow (hBM-MSCs) and cultured on the both nanoscaffolds. We evaluated the in-vivo effect of hBM-MSCs from both nanoscaffold cultures (cur - nanoscaffold/hMSCs and cur + nanoscaffold/MSCs) on liver fibrosis from its effective and preventive points and we assessed the mechanisms of these effects as in vitro studies as cell proliferation, its effect on hepatogenic differentiation, its effect on paracrine release of hBM-MSCs and in-vivo studying the effect on cell migration, survival, engraftment, fate of transplanted cells, modifying the fibrogenic and inflammatory microenvironments. Results: The results of animal model showed that single injection of preconditioning of hBM-MSCs using curcumin modified nanoscaffold ameliorate the fibrosis and prevent its recurrence until 24 weeks of therapy in contrast to improvement but not ameliorative effect of hBM-MSCs/ curcumin negative nanoscaffold which recurred progressively after 12 weeks of therapy. These effects of curcumin modified nanoscaffold were results from its highly efficacy on cell proliferation, in-vitro and in-vivo hepatogenic differentiation, increasing cell migration, engraftment and survival in the inflammatory microenvironment which was markedly improved by down regulation of inflammatory mediators and upregulation of anti-oxidant factors. Conclusion: hBM-MSCs cultured on the prepared curcumin nanomembrane in this study is promising in regenerative therapy for ameliorating the hepatic fibrosis and to prevent its recurrence.

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“…Stromal cells of adipose tissues have beneficial reparative/regenerative effects, since they contain somatic pluripotent MSCs [ 4 ], which are thought to be advantageous owing to their pluripotency as well as their immunomodulatory effects for the treatment of various injured organs, including cirrhotic livers [ 6 ]. Furthermore, autologous cells are relatively accessible and easy to obtain [ 20 ] from a patient's own adipose tissue; thus, the use of the freshly isolated autologous adipose tissue-derived stromal cells for reparation/regeneration therapy for injured organs is a practical approach [ 8 , [21] , [22] , [23] , [24] ]. However, it is necessary to characterize freshly isolated u-ADSCs from affected hosts and to determine their effects on cirrhotic liver.…”

Section: Discussionmentioning

confidence: 99%

Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair

Yano

Nasti

Seki

et al. 2021

Regenerative Therapy

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Introduction Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs), containing miscellaneous cells like the relatively abundant mesenchymal stem cells, are attractive for repair and regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH). Methods The NASH model was established by feeding C57BL/6J mice an atherogenic high-fat diet for 4 (NASH (4w)) or 12 weeks (NASH (12w)), followed by the isolation and characterization of u-ADSCs. Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by analyses of hepatic inflammatory cells, antigen profiles, fibrosis, and gene expression. Results Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences in surface antigen profiles. In NASH (4w) u-ADSCs, but not NASH (12w) u-ADSCs, the frequencies of the leukocyte markers CD11b, CD45, and CD44 were elevated; furthermore, we observed an increase in the M1/M2 macrophage ratio only in NASH (12w) u-ADSCs. Only in NASH-4w u-ADSCs, the expression levels cell cycle-related genes were higher than those in u-ADSCs. Wild-type u-ADSCs administered to mice with NASH-related cirrhosis decreased the infiltration of CD11b+, F4/80+, and Gr-1+ inflammatory cells, ameliorated fibrosis, and had a restorative effect on liver tissues, as determined by gene expression profiles and the NAFLD activity score. The therapeutic effects of NASH (4w) u-ADSCs and NASH (12w) u-ADSCs on NASH-related cirrhosis were highly similar to the effect of wild-type u-ADSCs, including reductions in inflammation and fibrosis. Conclusions NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH.

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Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy

Cited by 17 publications

References 28 publications

Stem cell-based therapy for human diseases

Stem cell-based therapy for human diseases

Curcumin Nanofiber PCL/PLGA/Collagen Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cells against Liver Fibrosis in Animal Model and Prevented its Recurrence

Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair

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