cell therapy in cv disease: future directions. 2 anversa p, nadal-ginard b et al. nature....
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Cell Therapy in CV Disease:Future Directions
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Anversa P, Nadal-Ginard B et al. Nature. 2002;415:240-3.
Cardiac renewal: Is the goal in sight?
“Remaining young at heart is a desirable but elusive goal. Myocyte regeneration may accomplish just that.
Continuous cell renewal in adult myocardium was thought to be impossible; multipotent stem cells may
be able to renew myocardium and, under certain circumstances, can be coaxed to repair
the broken heart after infarction.”
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Stem cell therapy: More questions than answers?
Routes of delivery Surgical vs percutaneous
Cell type and marker Myoblast vs BM CD 34/ AC133/ SP
Timing of delivery Acute vs chronic
Target patient population Best criteria
Cell origin Embryonic vs adult BM vs peripheral Culture expanded vs fresh
Courtesy of Timothy Henry, MD.
?Dose Dose response
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CCTRN: Addressing gaps in the knowledge baseNHLBI Cardiovascular Cell Therapy Research Network, established January 2007
Nat Clin Pract Cardiovasc Med. 2007;4:403.DCC = Data Coordinating CenterMHI = Minneapolis Heart Institute
Network DCC
Universityof Texas
Network DCC
Universityof Texas
University
of Florida
University
of Florida
Vanderbilt
University
Vanderbilt
University
ClevelandClinic
ClevelandClinic
MHIU of Minn
MHIU of Minn
Texas Heart
Institute
Texas Heart
Institute
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CCTRN: Goal and initial phase I/II clinical trials
Nat Clin Pract Cardiovasc Med. 2007;4:403.
Goal:Accelerate research into use of cell-based therapies in
management of CV diseases
TIME
Effect of timing of post-MI BMC
administration on measures of LV
function
Late TIME
Effect of late (2-3 weeks) post-MI BMC
administration on measures of LV
function
FOCUS
Effect of transmyocardial
BMC administration on measures of LV function in patients
with chronic IHD
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Year 02Year 01 Year 03 Year 05
PRC DSMB Review
Protocol 1 Development
Protocol 1
Protocol 2 Development
PRC DSMB Review
Protocol 2
Protocol 3 Development
Protocol 3
PRC DSMB Review
Courtesy Timothy Henry, MD.
CCTRN: Timeline of trials
Year 04
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Summary
• Current clinical efforts have focused in three overlapping areas: – Repair of myocardium after MI– Reconstitution of myocardium in setting of chronic HF– Therapeutic angiogenesis
• Promising early clinical experience with BMC, endothelial cells, and skeletal myoblasts
• Numerous questions regarding techniques and mechanism of benefit remain– Ongoing trials by the NHLBI CCTRN and other research groups
should provide insight