2018 saw accelerated understanding of the roles of stem cells in health and disease.  The Shruti Naik lab at the Rockefeller University Howard Hughes Institute demonstrated close interrelationship between immune cells and stem cells.  Stem cells store memories of prior activation by stress through specific epigenetic modifications that activate specific genes within stem cells. (1)  Chronic inflammatory diseases such as asthma may be driven by stem cell memories. Interleukins, key molecules controlling immune cells, appear to be drivers of the inflammatory responses since antibodies to cytokines block inflammatory responses.  Similar stem cell memories may underlie chronic gastric inflammation such as Crohn’s disease and irritable bowel disease. (2)

Vitro Biopharma supplies DVCStem (www.DVCStem.com) stem cells for an IRB-approved clinical trial of systemic inflammation that includes a large range of diseases such as multiple sclerosis (MS), Alzheimer’s disease (AD), injuries and other conditions.  Phase I results show an absence of adverse events and support efficacy.  Our trials include measurement of multiple inflammatory cytokine responses to stem cell therapy.  Our protocol consists of IV infusion of umbilical cord-derived MSCs produced in our c-GMP-compliant, FDA-registered, ISO9001:2015 Certified, & CLIA-registered lab.  Also during 2018, allogeneic MSC therapy was approved by the European equivalent of the FDA (EMA) for treatment of a form of Crohn’s disease.

Additional advances in 2018 support stem cell dysfunction as a cause of disease and foster the concept of stem cell diseases.  Osteoarthritis (OA) has been subject of extensive clinical testing in animals and humans.  Iijima and colleagues recently reviewed results of clinical testing in 2385 patients in 35 studies.  Therapy involves injection of expanded MSCs into the diseased joint. The results support safety and efficacy including pain reduction, recovery of function and regeneration of cartilage (3).  Reduction of stem cell function is thus likely an important factor in the development of OA.  Anti-aging trials showing reduction in frailty by MSC transplants also implicate stem cell dysfunction in age-related frailty, a major issue in geriatric medicine.  Further advances in 2018 showed specific reduction in anti-oxidative responses in MSCs derived from multiple sclerosis (MS) patients suggesting stem cell dysfunction may also be involved in development of MS (4).  There is also support for stem cell dysfunction as a causative factor in Alzheimer’s disease (AD). We postulate that stem cell therapy is effective by replacing dysfunctional patient stem cells that cause OA, MS, and age-related conditions such as AD.  Vitro Biopharma has ongoing and pending clinical studies of MSC therapy for MS, OA, PD and AD in addition to systemic inflammation.

By Jim Musick, Ph.D. President and CEO of Vitro Biopharma/Vitro Diagnostics, Inc.; Tiana Tonrey, MS, COO, Vitro Biopharma

References:

  1. Naik, S, et al, Two to Tango: Dialog between immunity and stem cells in health and disease. Cell 175: 908-920, 2018.
  2. Ordovos-Montanes, J, et al, Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560: 649-654, 2018.
  3. Iijima, H, et al, Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: Meta-analysis toward the establishment of effective regenerative rehabilitation. NPJ Regenerative Medicine 3:15-28, 2018.
  4. Redondo, J, et al, Dysregulation of mesenchymal stromal cell antioxidant responses in progressive multiple sclerosis. Stem Cells Translational Medicine 7: 748-758, 2018.