The field of regenerative medicine is at a ‘pivotal point’ in its development, according to a panel of experts speaking at the Bio meeting in Boston in June 2018. The past six months alone saw four new product approvals, which could be the ‘beginning of a large number of successes’, said moderator Morrie Ruffin, MD of the Alliance for Regenerative Medicine, which now has over 300 members.
Clinical results emerging from cell therapies over the next two years will be comparable with the successes seen with CAR-T cancer therapies, predicts Mike Scott, vp of product development at Toronto based Blue Rock Therapeutics, whose lead product uses pluripotent stem cells to grow new neurons that restore the lost dopamine function in Parkinsons patients.
‘The area of regenerative medicine allows us to do something audacious: to strive for cures. If you think of CAR-T and gene therapies, there’s every reason to say we can achieve the same with regenerative medicines,’ agreed Felicia Pagliuca, co-founder of Boston biotech Semma Therapeutics. Semma aims to replace the lost pancreatic beta cells of patients with Type 1 diabetes with their insulin producing equivalents grown in the lab. The technology is currently at preclinical stage.
Storing placental and cord blood cells at birth may no longer be necessary in the future, the researchers suggested. Traditional stem cell therapy approaches have used mesenchymal stem cells from these sources to regrow tissues and organs by differentiation into multiple cell types; however, newer technologies are increasingly making new cell types from ‘pluripotent’ stem cells generated directly from adult cells such as skin.
Frequency Therapeutics’ CEO David Luccino also spoke, for example, about the firm’s proprietary regeneration technology using small molecules to temporarily activate ‘progenitor cells’ already in the body, and which are the early descendants of stem cells that generally differentiate to produce only a specific cell type. Progenitor Cell Activation (PCA) Regeneration is claimed to avoid many of the problems of traditional cell or gene therapies by transiently causing innate progenitor cells to divide and differentiate to initiate repair, Luccino said - in a way similar to naturally regenerating tissues such as the skin and intestine.
The epithelium in the lower intestines is the fastest growing tissue in the body and regenerates itself every five days or so, he pointed out.
The approach is claimed to have the potential to yield a ‘whole new category of disease-modifying therapeutics’ from conditions including skin and GI disorders to diabetes and demyelination diseases. In 2017, researchers reported that small molecules identified by the firm could be successfully used to activate and produce large colonies of progenitor cells able to grow and regenerate damaged cochlear hair cells – heralding a potential cure for a leading cause of hearing loss (C&I, 2018, 4, 19; Cell Rep, doi: 10.10161j.celrep.2017.01.066).
A Phase 1 trial completed at the end of 2017 and a Phase 2 trial is planned for later in 2018, while in May 2018 the company was awarded a $2m grant from the US Department of Defense to investigate the potential of the technology to restore hearing loss among military service personnel.
In another departure from traditional stem cell medicine, meanwhile, Steve Stice, CEO of ArunA Biomedical, also emphasised the power of harnessing exosomes – extracellular vesicles present in biological fluids such as blood and urine and cell culture media – particularly as drug delivery vehicles for cell therapies. Since their discovery more than 30 years ago, the company reports that nanometre-sized exosomes have been increasingly found to play a role in cellular communication, capable of delivering functional proteins, mRNA transcripts and miRNA to cells throughout the body. ‘Coming years will see exosomes playing a major role in regenerative processes,’ he predicts. Continuous development will see exosomes in the clinic in the next two years whereupon the field will steamroller and explode.’
In April, ArunA announced new data showing that the company’s exosomes – derived from neural stem cells – improved the recovery of pigs that had experienced stroke (https://doi.org/10.1161/STROKEAHA.117.020353). The proof-of-concept study follows an earlier successful study in mice reported in January 2018, and is significant because the pig brain is architecturally similar to the human brain, Stice said. ‘Like the human brain, the pig brain contains more than 60% white matter, the tissue most vulnerable to pathological processes that follow ischemic stroke.’
ArunA hopes its technology will lead to a cell-free treatment for stroke, which it says is the leading cause of long-term disability in the US. The company’s manufacturing methods allow it to make billions of cells and up to trillions of exosomes per manufacturing lot, it reports. In addition to the stroke study, there are plans for preclinical studies in epilepsy, traumatic brain injury and spinal cord injuries in 2018.
Finally, Antonio Regalado, senior editor of MIT Technology Review, summed up the current state of play in the regenerative medicine area when he cited another expert who commented that the ultimate objective was ‘mastery over cell fate…I can’t predict what the field will bring but there’s nothing more profound than starting from the fertilised egg and being able to control its destiny.’