Evaluation of regenerative pontential of cardiomyocytes derived from iPSCs in pigs

• Grant number: 21/01413-3
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: June 01, 2021
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Estela Mitie Cruvinel
• Grantee: Estela Mitie Cruvinel
• Company: Pluricell Biotech Pesquisa e Desenvolvimento Ltda. - ME
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: São Paulo
• Pesquisadores principais: Julliana Carvalho Campos de Oliveira ; Rafael Dariolli
• Associated researchers: Antonio Fernando Ribeiro Júnior ; Sirlene da Silva Rodrigues

Abstract

Stem Cells have been largely studied for its potential in the field of regenerative medicine. This area of medicine is seen with optimism by the scientific community because it can address many chronic problems that, for a long time, has affected a large portion of the population and do not have cures (in traditional small molecule medicine). Many studies have investigated the clinical potential of a wide range of stem cells with the goal of understanding their true impact in patients. Cardiovascular diseases are the most frequent cause of death in the world accounting for more than 1/3 of all deaths every years. Acute myocardial infarction (AMI) is a astonishingly common event with an incidence of approximately 700k cases per year only in the US (https://www.cdc.gov/heartdisease/heart_attack.htm). Since the heart has a very low regenerative capacity, the tissue cannot replenish itself after an injury and has its function compromised. Some patients after are breathless at rest and survival is ~80% in the first year, comparable to most aggressive cancers. It is estimated that in a AMI, the patients loses the equivalent of 1b heart cells. There are two kinds of evidence in the scientific literature to support quality of heart cells derived from iPSCs produced in the lab for therapeutic applications: 1) evidence of engraftment with unequivocal demonstration of exogenous human tissue in the transplanted animal and 2) evidence of functional improvement of the heart which received the cells (efficacy). Usually, the former tests (engraftment) are performed in small animals (rats and mice) due to their easy handling in large quantities and relatively low costs. The latter tests (efficacy) are generally performed in large animals (pigs or monkeys) due to their similarity of the cardiovascular systems to humans. While in small animals (~50-60 rats) the quantity of cells injected per animal is in the range of 10m/rat (a complete study needs 100-200 million cells) with a final cost of about ~200 thousand reais, a large animal study (~10 pigs) we forecast around 800-900 million cells/animal with a final cost of around 1.3 million of reais. In the last years, a solid body of evidence has been formed in different labs around the world which show that heart cells derived from iPSCs and produced in the lab are able to engraft and improve overall heart function of animals injected with them after myocardial infarction, either small or large. In the same way, PluriCell Biotech, since 2013, has put a stong effort since 2013 to be able to produce human heart cells (Pipe phase 1 - 2013/50076-3) and characterize them (Pipe phase 2 - 2015/50224- 8). Recently, we announced a private investment made in the company of 1.1 million USD from one of the largest pharmaceutical companies (LIBBs) to execute a project that evaluates the therapeutic potential of these cells in small animals and, preliminarily, in large animals (pigs) This project has the goal of supporting a large-scale study in pigs (>10 animals) to evaluate the efficacy of cardiac cells produced from iPSCs by PluriCell injected in pigs previously infarcted and immunosuppressed. In the end, the results will give support as a proof of concept study for pivotal studies submitted to regulatory agencies. (AU)