While stem cell transplants are clearly warranted for certain conditions including leukemia & lymphoma, there is growing evidence that activation of endogenous stem cells is an emerging approach to therapy. Latent stem cells require activation of specific biological signaling pathways including mobilization through chemokine signaling, proliferation/differentiation through Wnt pathway activation and epigenetic modulation of specific gene expression to become therapeutic. Preclinical studies suggest efficacy of stem cell activation in traumatic brain injury (TBI), AD, Parkinson’s, ALS and spinal cord injury.  Also, this approach may be appropriate therapy for inflammatory/autoimmune conditions including Crohn’s disease, MS, and several other conditions as well.  Furthermore, recruitment of adult stem cells is associated with enhanced learning of perfect pitch (1) and muscle function can be enhanced in mice by administration of GDF11, a stem cell activation agent.  Thus, endogenous stem cell activation may not only be therapeutic but also used to enhance performance and possibly, longevity. (2)

Stem cell activation awakens innate stem cell systems to optimize healing, cellular regeneration and functionality.  This approach has numerous advantages over stem cell transplantation including innately autologous therapy without acute or long-term complications from introduction of allogeneic cellular materials.  The approach involves administration of an activating agent or agents and effects are controlled by dosage/pharmacokinetics of the stem cell mobilizing, epigenetic or proliferative agents thus avoiding transplantation issues including possible cellular modification during expansion, contamination, etc.  The pathway to regulatory approval is shorter and less costly since certain combinations of generic drugs may be effective and there are natural substances exhibiting apparent efficacy.  Also, new drug targets are associated with this paradigm, such as specific combinations of proliferation and epigenetic agents.

Vitro Biopharma has been pursuing this approach for the past six months using patients treated within a clinical network. This network is managed by a well-known immunologist, Professor Josef Smarda, who has a team of professional experts that operate the clinics and administer treatment of these patients. The primary approach is to resolve toxicity, infectivity and specific deficiencies thus restoring physiological conditions while monitoring clinical status. Optimum cellular functionality is viewed as a necessary condition to elicit therapeutic benefit from activation of endogenous stem cells. We also use proteomic arrays to quantify various cytokines, growth factors and neurotrophins to develop disease profiles.  We establish baseline results and are now testing agents known to activate stem cells to determine effects on the biomarker disease profile as well as clinical status.  We are also developing additional biometric analysis of stem cell activation including MSC mobilization to peripheral blood, serum content of key stem cell biomarkers and tools for imaging of stem cell activation.

Vitro Biopharma is nearing commercialization of stem cell-based assays utilizing live cell imaging of cell migration, proliferation and reprogramming for drug discovery and support of clinical trials. We are also developing a clinical trial testing of stem cell activation for treatment of TBI and advanced molecular diagnostics while developing new stem cell activators.  Vitro Biopharma is committed to further development and testing of the activation of latent, internal stem cells since this approach is widely supported by pre-clinical research and obviates several problematic issues associated with the transplantation of adult stem cells.

By Jim Musick, Ph.D. President and CEO of Vitro Biopharma/Vitro Diagnostics, Inc.

References:

1. Gervain, J, et al., Front Syst Neurosci 7: 102, 2013

2. Sinha, M. et al., Science 344: 649, 2014