Reinfusion of highly purified CD133⁺ bone marrow-derived stem/progenitor cells in patients with end-stage liver disease: A phase I clinical trial

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• 作者：Pietro Andreone^a ; ^{pietro.andreone@unibo.it" class="auth_mail" title="E-mail the corresponding author} ; Lucia Catani^b ; Cristina Margini^a ; Lucia Brodosi^a ; Stefania Lorenzini^a ; Daria Sollazzo^b ; Benedetta Nicolini^b ; Rosaria Giordano^c ; Tiziana Montemurro^d ; Simonetta Rizzi^b ; Elisa Dan^b ; Valeria Giudice^e ; Mariele Vigan&ograve ; ^d ; Andrea Casadei^f ; Francesco G. Foschi^g ; Deborah Malvi^h ; Mauro Bernardi^a ; Fabio Conti^a ; Roberto M. Lemoliⁱ
• 关键词：Cirrhosis ; Haematopoietic stem/progenitor cells ; Regenerative medicine ; Stem cell therapy
• 刊名：Digestive and Liver Disease
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：47
• 期：12
• 页码：1059-1066
• 全文大小：1395 K

文摘

Bone marrow stem/progenitor cells seem to be effective in liver regeneration after tissue injury.

Aim

To evaluate the feasibility and safety of the mobilization and reinfusion of CD133⁺ stem/progenitor cells in patients with end-stage liver disease.

Methods

Autologous CD133⁺ stem/progenitor cells, mobilized with granulocyte-colony stimulating factor, were collected by leukapheresis and reinfused at increasing doses through the hepatic artery starting from 5 × 10⁴/kg up to 1 × 10⁶/kg.

Results

16 subjects with Model for End-stage Liver Disease (MELD) score between 17 and 25 were enrolled, 14 mobilized an adequate number of CD133⁺ stem/progenitor cells and 12 were reinfused. No severe adverse events related to the procedure were reported. MELD score significantly worsened during mobilization in Child Turcotte Pugh-C patients. A significant improvement of liver function was observed 2 months after reinfusion (MELD 19.5 vs 16; P = 0.045). Overall, 5 patients underwent liver transplantation within 12 months from reinfusion and 2 died because of progressive liver failure.

Conclusions

CD133⁺ stem/progenitor cells reinfusion in patients with end-stage liver disease is feasible and safe. A worsening of liver function was observed during mobilization in Child Turcotte Pugh-C patients. The temporary improvement of MELD score after reinfusion suggests that stem cells therapy may be a “bridge to transplant” approach for these patients.