Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis

Phase 2 trial

Ki Tae Suk, Jung Hwan Yoon, Moonyoung Kim, Chang Wook Kim, Ja Kyung Kim, Hana Park, Seong Gyu Hwang, Dong Joon Kim, Byung Seok Lee, Sae Hwan Lee, Hong Soo Kim, Jae Young Jang, Chang Hyeong Lee, Byung Seok Kim, Yoon Ok Jang, Meeyon Cho, Eun Sun Jung, Yong Man Kim, Si Hyun Bae, Soonkoo Baik

Research output: Contribution to journalArticle

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Abstract

Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).

Original languageEnglish
Pages (from-to)2185-2197
Number of pages13
JournalHepatology
Volume64
Issue number6
DOIs
Publication statusPublished - 2016 Dec 1

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Alcoholic Liver Cirrhosis
Autologous Transplantation
Mesenchymal Stromal Cells
Mesenchymal Stem Cell Transplantation
Bone Marrow
Liver Cirrhosis
Fibrosis
Biopsy
End Stage Liver Disease
Liver Function Tests
Gastroenterology
Collagen
Alcohols
Staining and Labeling
Safety
Control Groups
Injections
Liver
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Suk, Ki Tae ; Yoon, Jung Hwan ; Kim, Moonyoung ; Kim, Chang Wook ; Kim, Ja Kyung ; Park, Hana ; Hwang, Seong Gyu ; Kim, Dong Joon ; Lee, Byung Seok ; Lee, Sae Hwan ; Kim, Hong Soo ; Jang, Jae Young ; Lee, Chang Hyeong ; Kim, Byung Seok ; Jang, Yoon Ok ; Cho, Meeyon ; Jung, Eun Sun ; Kim, Yong Man ; Bae, Si Hyun ; Baik, Soonkoo. / Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis : Phase 2 trial. In: Hepatology. 2016 ; Vol. 64, No. 6. pp. 2185-2197.
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title = "Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial",
abstract = "Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25{\%} (19.5 ± 9.5{\%} versus 14.5 ± 7.1{\%}) and 37{\%} (21.1 ± 8.9{\%} versus 13.2 ± 6.7{\%}) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).",
author = "Suk, {Ki Tae} and Yoon, {Jung Hwan} and Moonyoung Kim and Kim, {Chang Wook} and Kim, {Ja Kyung} and Hana Park and Hwang, {Seong Gyu} and Kim, {Dong Joon} and Lee, {Byung Seok} and Lee, {Sae Hwan} and Kim, {Hong Soo} and Jang, {Jae Young} and Lee, {Chang Hyeong} and Kim, {Byung Seok} and Jang, {Yoon Ok} and Meeyon Cho and Jung, {Eun Sun} and Kim, {Yong Man} and Bae, {Si Hyun} and Soonkoo Baik",
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Suk, KT, Yoon, JH, Kim, M, Kim, CW, Kim, JK, Park, H, Hwang, SG, Kim, DJ, Lee, BS, Lee, SH, Kim, HS, Jang, JY, Lee, CH, Kim, BS, Jang, YO, Cho, M, Jung, ES, Kim, YM, Bae, SH & Baik, S 2016, 'Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial', Hepatology, vol. 64, no. 6, pp. 2185-2197. https://doi.org/10.1002/hep.28693

Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis : Phase 2 trial. / Suk, Ki Tae; Yoon, Jung Hwan; Kim, Moonyoung; Kim, Chang Wook; Kim, Ja Kyung; Park, Hana; Hwang, Seong Gyu; Kim, Dong Joon; Lee, Byung Seok; Lee, Sae Hwan; Kim, Hong Soo; Jang, Jae Young; Lee, Chang Hyeong; Kim, Byung Seok; Jang, Yoon Ok; Cho, Meeyon; Jung, Eun Sun; Kim, Yong Man; Bae, Si Hyun; Baik, Soonkoo.

In: Hepatology, Vol. 64, No. 6, 01.12.2016, p. 2185-2197.

Research output: Contribution to journalArticle

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T1 - Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis

T2 - Phase 2 trial

AU - Suk, Ki Tae

AU - Yoon, Jung Hwan

AU - Kim, Moonyoung

AU - Kim, Chang Wook

AU - Kim, Ja Kyung

AU - Park, Hana

AU - Hwang, Seong Gyu

AU - Kim, Dong Joon

AU - Lee, Byung Seok

AU - Lee, Sae Hwan

AU - Kim, Hong Soo

AU - Jang, Jae Young

AU - Lee, Chang Hyeong

AU - Kim, Byung Seok

AU - Jang, Yoon Ok

AU - Cho, Meeyon

AU - Jung, Eun Sun

AU - Kim, Yong Man

AU - Bae, Si Hyun

AU - Baik, Soonkoo

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).

AB - Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).

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