A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Hepatic Fibrosis

Abstract

Liver cirrhosis is the 6th leading cause of death in adults aged 15–59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use – namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs) in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, “A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study.” The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.

Serelaxin enhances the therapeutic effects of human amnion epithelial cell‐derived exosomes in experimental models of lung disease

“…The same could be applied to pirfenidone for the treatment of pulmonary fibrosis, as pirfenidone primarily targets interstitial fibrosis ( Figure 3b) and can also be associated with several side effects when therapeutically administered (Jiang et al, 2012). As AECs (Lim, Hodge, Moore, Wallace, & Sievert, 2017), exosomes (ClinicalTrials.gov Identifier NCT02138331; NCT03384433), and serelaxin (Teerlink et al, 2013) have separately been evaluated in clinical trials, novel strategies incorporating this combination therapy can be fast-tracked for human trials.…”

Phase 1 Trial of Amnion Cell Therapy for Ischemic Stroke

“…No severe adverse events were found to be associated with hAEC treatment. A Phase 1 trial of hAECs in adults with compensated cirrhosis is also underway in our institution ( 21 ) (ACTRN12616000437460).…”

“…The Cell Therapies and Regenerative Medicine Platform (CTRMP) at the Monash Health Translation Precinct has a cryobank of isolated, screened, and stored hAECs for clinical trial use ( 21 ). These cells are routinely obtained from healthy women with a healthy singleton pregnancy undergoing an elective cesarean section at term and donating their placenta for clinical trial purposes with informed consent.…”

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

“…It is uncertain, if the changes induced in the cell genome would not cause further spontaneous mutations leading to cancer. However, such concerns are not raised by the use of amnion epithelial cells [11] and, as it can be assumed, HLC obtained from them. Preclinical studies on mice [14,113] using HLC obtained from hAEC have shown, that their use in the treatment of liver failure in humans does not require the use of immunosuppressive treatment [13].…”

“…placenta and umbilical cord are abundant sources of cells, that meet the biological criteria of good transplantable material, and can be isolated in a manner that does not raise moral and ethical controversies. Some of afterbirth cell populations are successfully used in clinical trials, including the treatment of type 1 diabetes, systemic lupus erythematosus and ischemic stroke [6][7][8][9][10][11]. Both in vivo and in vitro studies have shown that cells derived from these sources, e.g.…”