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What Regenerative Medicine Research is the John Paul II Medical Research Institute Conducting for Lung Disease? Part 1

Creating a Pipeline of Adult Stem Cells to Address the Paracrine Challenge-While There is a Lack of Current Innovation for COPD Patients

by Dr. Alan Moy, November 14, 2018

The first cardinal rule in drug development is to protect against what you don't know and prepare for the ultimate surprises that come along the way. There is a 70-90 percent chance of failure with any one drug candidate. This means that statistically one needs at least 7 drug candidates to achieve one drug's success. In the case of regenerative medicine, this means that one needs backup plans in the event of any failures. Since lung disease (or any other disease frankly) is regulated by cycles of inflammation, cell death and scarring (hallmarks of chronic lung disease), we need to ask the fundamental question, “What source of stem cells would offer the greatest protection against these effects?” The first place to find that answer is to look towards observations found in nature. The best example found in nature is the biology that exists between fetus and mother. The immune system of the two are not identical, and because of this dissimilarity, one would expect that the mother's immune system would attack the fetus. However, this is obviously not the case because we would otherwise be an extinct species. Thus, there must be some protective biology outside the fetus and mother that protects against the maternal immune system. There is now experimental data that the placenta, umbilical cord and umbilical cord blood protect the fetus during development. Another interesting observation is that fetuses never develop scars. Thus, there must be something within the mother's womb that displays some anti-scarring property. There is now good scientific evidence that stem cells from these postnatal tissues afford these properties. Further, postnatal tissues offer more stem cells than any other tissue source. There are at least 6 well described stem cells from these sources:

1. From umbilical cord blood: CD34+, CD133+ cells and multipotent stem cells.
2. From umbilical cord tissue: Wharton jelly mesenchymal stem cells.
3. From placental tissue: amniotic membrane mesenchymal stem cells and placenta-derived epithelial stem cells.

Collectively, these postnatal stem cells are ideal for cell transplantation for several reasons (and some are already in clinical trials around the world for a variety of diseases): (1) They are immunologically naive (i.e. low chance for rejection; (2) They are the most robust and the healthiest because they are the youngest; (3) They are free of long-term exposure to environmental toxins (e.g. smoking, alcohol and carcinogens); and (4) They are readily available from discarded tissue from newborn deliveries, of which there are over 1 million births per year in the U.S. alone. Some of these stem cells have a predisposition to treat certain diseases better than others. Some can grow under artificial conditions to higher levels than others (e.g. cord blood derived multipotent stem cells can provide 7 million doses from one delivery alone); and some have more complicated growth requirements. There is evidence that the paracrine activity of these stem cells is greater than BM-MSC which was highlighted in the last post. Further, these postnatal stem cells have the capability to be genetically reprogrammed into induced pluripotent stem cells (iPSC), which can become any cell found in the body. Ironically, the controversy surrounding abortion which destroys life, represents the very tissue that we will need to treat human disease to save lives as we age.

The good news is that over the past decade, John Paul II Medical Research Institute (JP2MRI) has contributed to research that has led to developing each of these stem cells. The Institute has the largest portfolio of postnatal stem cells in the world. This research subsequently facilitated commercial manufacturing to where these stem cells are now used in medical research around the globe based on the Institute's effort (financial disclosure – Dr. Moy is the CEO of Cellular Engineering Technologies, a biotechnology company, that now manufactures these stem cells). Our consortium is the sole source manufacturer for some of these stem cells, and sole source manufacturer for government agencies like the US Navy.

The Institute is now poised to examine which of these stem cells have the best paracrine activity to treat lung disease. This requires developing methods to grow up large batches of these stem cells and separate out the microvesicles from the stem cells. There are two therapeutic approaches which can be attempted using these stem cells: 1) Administer the stem cells whole, with the belief that the stem cells will home to the site of disease and deliver their microvesicle cargo; or 2) Purify the microvesicles from stem cells and administer the microvesicles (as a cell-free method) directly to the site of disease by either intravascular route, inhalation or by bronchoscopy. There are advantages and disadvantages to both approaches.

Thus, having access to multiple different stem cells mitigates against the statistical risk of failure inherent in drug development. With 6 postnatal stem cells, each of which can also be converted into iPSC, this translates into 12 potential stem cell therapies and 12 microvesicle cell-free therapies. Thus, with 24 potential regenerative medicine therapies, it is anticipated that the odds of success are high that at least one regenerative medicine will be successful. Additionally, the Institute has also considered using a backup plan of combining synthetic biology with these stem cells (information that will be presented in later posts).

The prior discussion highlights regenerative medicine solutions that may offer cell protection and cell repair possibilities for lung disease and other disorders. However, they may not be sufficient solutions for replacing the alveolar cells that are lost in COPD or replace critical cells for repairing other organs (e.g. beta cells of the pancreas in juvenile diabetes). Under that circumstance, we also need a novel pluripotent stem cell. As mentioned in the prior post, we need a pluripotent stem cell that is devoid of ethical controversy, potent and has much lower risk of neoplasm. That research will be presented in Part 2.

Based on historic timelines and cost, the Institute estimates that it will take 5 years and 10 million dollars (2 million dollars per year) to complete the FDA-required preclinical research to launch the first regenerative medicine clinical trial in COPD. According to the World Health Organization, there are 65 million individuals around the world that live with moderate to severe COPD. If only 100,000 of these 65 million were to commit to donating $20 a year, this goal would be met. That translates to sacrificing 2 packs of cigarettes per year.

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