Research Projects

Cell Matrix ArraysTM.

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CiPSTM Cells.

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Enhanced Bone Marrow Stem (EBMSTM) Cells.

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Predictive Toxicity Assays.

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Quantum Dot Lateral Flow Microarray Dipstick for Agricultutral Diagnostics.

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  Project Overview


Enhanced Bone Marrow Stem (EBMSTM) Cells.

Human bone marrow cells (BMCs) have been used as a source for autologous and allogenic cell therapies. We have used our biomaterial microarray hydrogel microenvironment niche high throughput screening technology, Cell Matrix Arrays (CMATM), to develop ideal hematopoietic modeled microenvironment niche for ex-vivo maintenance and enhancement of human BMCs. Human Enhanced Bone Marrow Stem (EBMS) cells have so far been successfully validated in cellular and animal models of cardiovascular regenerative cell therapy (see below).

Cardiovascular Regenerative Cell Therapy.

Heart failure principally caused by ischemic heart disease is common and its prevalence is increasing worldwide (1). Contrary to previous understandings, myocardium continuously regenerates throughout life with an increased rate of regeneration after large myocardial infarctions (2). This regeneration is, however, limited to the viable myocardium and its border zone. Additionally, there is a net loss of cardiomyocytes during myocardial infarction, resulting in the remodeling and the impairment of cardiac-pump function (3, 4). Early reperfusion therapy results in myocardial salvage and significant reduction of early mortality rates (5). However, post-infarction heart failure due to ventricular remodeling remains a major problem (6). Enhancement of the regeneration of cardiomyocytes has been shown to stimulate neovascularization of the infracted area, reversing post-infarction heart failure (7-11).

Bone marrow harbors adult stem cells and progenitor cells with vast differentiation potential including the capability for solid-organ repair (12, 13). In animal models of myocardial infarction, intramyocardial or intravenous injections of bone marrow derived cells (BMC) have shown improved left ventricular function angiogenesis, reduced apoptosis, and reduced remodeling (14, 15). Human clinical pilot studies have shown that intracoronary infusion of BMC is feasible and beneficially affects post-infarction remodeling processes in acute myocardial infarction (AMI) patients (8-11, 18, 19).

For updates on progress please refer to our R&D Projects page. For collaborations email us at TAP@dnamicroarray.com.

References

  1. 2001 Heart and stroke statistical update. Dallas : American Heart Association, 2000. Braunwald E. Cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997;337:1360-9.
  2. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750-7.
  3. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation 1990;81:1161-72.
  4. Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation 2000;102:Suppl 4:IV-14–IV-23.
  5. Lange RA, Hillis LD. Reperfusion therapy in acute myocardial infarction. N Engl J Med 2002;346:954-5.
  6. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000;101:2981-8.
  7. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913-8.
  8. Assmus B, Schachinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 2002;106:3009-17.
  9. Britten MB, Abolmaali ND, Assmus B, et al. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 2003;108: 2212-8.
  10. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141-8.
  11. Schachinger V, Assmus B, Britten MB ,. et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004;44:1690-9.
  12. Korbling M, Estrov Z. Adult stem cells for tissue repair — a new therapeutic concept? N Engl J Med 2003;349:570-82.
  13. Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, Ratajczak J. Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells ‘hide out’ in the bone marrow. Leukemia 2004;18:29–40.
  14. Fuchs S, Baffour R, Zhou YF, et al. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 2001;37:1726-32.
  15. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430-6.
  16. Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001;107:1395-402.
  17. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701-5.
  18. Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001;108:391-7.
  19. Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001;103:2885-90.


 
 
 
 

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