Technology

Our Stem Cells

CardioCell has an exclusive worldwide license from Stemedica Cell Technologies Inc. to use its itMSCs (ischemia-tolerant mesenchymal stem cells) for the exploration of therapeutic cardiovascular indications.

The itMSC Advantage

itMSCs (ischemia-tolerant mesenchymal stem cells) are the “trophic” cells in stem cell treatment; they work primarily on the environment for healing. Circulating throughout the body and homing to sites of injury, they release growth factors into the damaged tissue, rescuing damaged cells from death and creating the right conditions for the newly mobilized cells to proliferate and repair. Stemedica has an inventory of these itMSCs that are being used in clinical trials domestically and internationally under the control of regulatory agencies.

Stemedica’s BioSmart Technology Platform™ isolates, extracts, expands, manufactures and master banks unique lines of immune-privileged adult stem cells. The distinctive properties of these itMSCs are unsurpassed in the industry and include the following attributes:

  • Ischemia and toxin tolerant: itMSCs are manufactured in hypoxic environments and specifically formulated to combat ischemic conditions. These cells are secreting factors such as VEGF and SDF-1 that is thought to enhance the healing process. VEGF is critical for new blood vessel growth and SDF-1 helps prevent cellular death.
  • Immune privileged: itMSCs do not exhibit HLA proteins that cause rejection. Independent biosafety labs test all cell types to confirm the lack of HLA expression. No immunosuppressant agents are required during transplantation.
  • Documented safety: All cells undergo rigorous testing for infectious disease, acute and chronic toxicity and tumorigenicity.
  • Established purity: Stemedica maintains rigorous specifications for each of the appropriate biological markers that indicate cell purity. Furthermore, extensive batch testing indicates lot-to-lot reproducibility.
  • Validated potency: For stem cells to be effective in vivo (in the human body), they must secrete the appropriate growth factors, cytokines and hormones. The stem cells must also demonstrate the ability to differentiate into specific types of tissues, i.e. bone, neurons or cartilage. itMSCs meet these criteria.
  • Fully characterized: Each of Stemedica’s stem cell products is thoroughly analyzed in terms of gene analysis and protein profile.
  • Ability to mobilize host progenitor cells: itMSCs help mobilize the body’s resources in the regenerative process.

The Allogeneic Stem-Cell Difference

There are two types of cells currently used in the cardiology field: autologous and allogeneic. Autologous stem cells derive from the bone marrow of the patient that is treated. They are retrieved surgically, expanded, and transplanted back into the same patient’s myocardium or bloodstream. Allogeneic stem cells derive from the bone marrow of healthy volunteers. These cells are expanded and stored for future use in many other patients. Leveraging these allogeneic itMSCs, CardioCell delivers the following competitive advantages:

1) Reproducibility: Stemedica can produce 600,000 doses of itMSCs from one individual donor, while maintaining strict manufacturing control over cell quality and performance.

2) Immune Privilege: Autologous cells were considered more immune privileged than allogeneic cells that derive from the same organism, thus not causing immune responses. The main cause of rejection and clearance of allogeneic stem cells from the host is expression of HLA-DR receptor on the surface, which leads to immune responses from the host organism. itMSCs are grown under low-oxygen conditions; this reduces the presence of HLA-DR to less than 2 percent therefore reducing the chance of immune response.

3) Cost: Autologous stem-cell administration is much more expensive than allogeneic alternatives. Allogeneic cells are available off-the shelf and already tested, but autologous cells must be retrieved from the patient by invasive surgical procedure, tested, expanded individually and, finally, re-introduced into the patient.

4) Scalability: itMSCs are highly scalable with 600,000 doses deriving from a single healthy donor. Autologous cells are not scalable because they need to be retrieved surgically from each individual patient.

5) Non-Invasiveness: As described above, CardioCell uses off-the-shelf cells and administers them non-invasively via intravenous injection. In contrast, autologous cells must be collected through invasive procedures.

6) Quality Control: Each time autologous cells are retrieved they represent different pool of cells, which raises safety concerns. Allogeneic itMSCs have passed all quality-control and Phase I clinical-trial safety testing.

7) Autologous vs. Allogeneic – prior studies: To some extent bone marrow-derived MSCs are immunoprivileged, and allogeneic MSCs might elude elimination by the host immune system because they do not express MHC class II receptors and only low levels of MHC class I receptors1. As with endothelial progenitor cells2, MSCs are subject to age- and disease-related changes3,4,5, decreasing in number in the bone marrow with age5,6. Although terminal differentiation is preserved in older MSCs7, it is weaker when compared to younger cells8,9. The gene-expression profile of aging MSCs shows increased abundance of differentiation- and growth-arrest-related transcripts and down-regulation of transcripts involved in RNA processing3. Moreover, these MSCs did not improve cardiac function10These findings support the concept that allogeneic MSCs from young donors may have greater regenerative capacity than autologous cells from older subjects with CAD. 

So far, allogeneic cells are the only ones that showed hope in both acute myocardial infarction and chronic heart failure indications.

  1. Grinnemo KH, Mansson A, Dellgren G, et al. Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. J Thorac Cardiovasc Surg 2004;127:1293-300.
  2. Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 2004;109:1615-22.
  3. Hacia JG, Lee CC, Jimenez DF, et al. Age-related gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells. J Cell Biochem 2008;103:1198-210.
  4. Kasper G, Mao L, Geissler S, et al. Insights into mesenchymal stem cell aging: involvement of antioxidant defense and actin cytoskeleton. Stem Cells 2009;27:1288-97.
  5. Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev 2006;5:91-116.
  6. Tokalov SV, Gruner S, Schindler S, Wolf G, Baumann M, Abolmaali N. Age-related changes in the frequency of mesenchymal stem cells in the bone marrow of rats. Stem Cells Dev 2007;16:439-46.
  7. Roura S, Farre J, Soler-Botija C, et al. Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells. Eur J Heart Fail 2006;8:555-63.
  8. Fan M, Chen W, Liu W, et al. The effect of age on the efficacy of human mesenchymal stem cell transplantation after a myocardial infarction. Rejuvenation Res 2010;13:429-38.
  9. Tokalov SV, Gruener S, Schindler S, Iagunov AS, Baumann M, Abolmaali ND. A number of bone marrow mesenchymal stem cells but neither phenotype nor differentiation capacities changes with age of rats. Mol Cells 2007;24:255-60.
  10. Zhang H, Fazel S, Tian H, et al. Increasing donor age adversely impacts beneficial effects of bone marrow but not smooth muscle myocardial cell therapy. Am J Physiol Heart Circ Physiol 2005;289:H2089-96.