Mesenchymal stromal cell therapy for liver fibrosis

Haldar, Debashis (2019). Mesenchymal stromal cell therapy for liver fibrosis. University of Birmingham. Ph.D.

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Abstract

Substantial uncertainty exists from pre-clinical liver fibrosis models as to whether mesenchymal stromal cells (MSCs) are anti-fibrotic, and yet clinically they have been proposed as a putative anti-fibrotic therapy for patients. This research was set out to examine whether MSC therapy can reduce liver fibrosis.

An assessment of the depth and persistence of fibrosis in two murine liver fibrosis models (12 doses of intraperitoneal carbon tetrachloride, or 16 weeks of oral thioacetamide) allowed a statistically powered analysis of MSC intervention. Human umbilical cord MSCs were peripherally injected after liver fibrosis was established, or during fibrogenesis. Finally, the effect of MSC conditioned medium on the biology of human stellate-cell line, LX2 cells, was examined.

MSC administration neither resolved established fibrosis, nor abrogated fibrogenesis in either model. Peripherally injected MSCs were sequestered in the lungs. However, MSC conditioned medium attenuated the expression of collagen type-1 mRNA and promoted apoptosis in LX2 cells. The discordance between the in vivo and in vitro findings requires further exploration. Nevertheless, this statistically powered robust examination of human umbilical cord MSCs suggests no discernible anti-fibrotic influence in vivo, and future testing would require a significant deviation in protocol to overcome a documented barrier from this research.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):