Biomaterial strategies to improve the efficacy of bone marrow cell therapy for myocardial infarction

ABSTRACT

Introduction: The feasibility and safety of bone marrow cell (BMC) therapy for cardiac repair following myocardial infarction has been demonstrated in clinical studies, albeit with relatively modest structural and functional benefits. In response to the shortcomings of BMC therapy, the use of biomaterials to enhance cell transplantation is being investigated.

Areas covered: The authors first review what has been learned from BMC therapies for the treatment of myocardial infarction in animal models and in clinical trials. Some issues that may be limiting the efficacy of BMC therapy are then described. Lastly, they summarize several biomaterial approaches that have been reported to improve transplanted cell retention and functional outcome, and then focus on how a material can enhance cell function such as proliferation, viability, endothelial differentiation and angiogenic potential.

Expert opinion: Improvements are needed if BMC therapy is to become a viable treatment in the clinic. There is optimism that a biomaterial strategy will lead to superior results compared to the cell therapy alone. Through the identification of underlying cell-biomaterial mechanisms, the establishment of comparative standards, and an awareness of the lessons learned from cell therapy trials, biomaterial-enhanced BMC therapy may become an option for the treatment of heart disease patients.

KEYWORDS:

• Biomaterials
• bone marrow cells
• cell homing
• cell therapy
• engraftment
• myocardial infarction

Article highlights

• The number and function of BMCs that are mobilized post-MI are predictive of functional recovery and future cardiovascular events, suggesting that BMC therapy may help improve post-MI outcomes.

• BMC therapy has been shown to improve the function of the MI heart in animal models through direct contribution to regenerating tissue and through paracrine signaling mechanisms. In the clinic, the feasibility and safety of BMC therapy has been established, but the functional outcomes have been less than expected.

• The lack of more significant functional restoration in clinical trials of BMC therapy has been attributed to the low survival and function of the transplanted cells; therefore BMC therapy would benefit from new strategies to improve its efficacy.

• Using various tissue engineering approaches, biomaterials have been developed with the aim of improving the homing, retention, engraftment and survival of BMCs transplanted for treatment of the MI heart.

• Biomaterials can also be designed with specific properties (e.g. ligands, growth factors loaded) to promote the proliferation, viability, endothelial differentiation, paracrine signaling and migration of BMCs, thus improving their therapeutic potential.

• Through the careful design of future studies, a better understanding of cell-biomaterial interactions and the establishment of comparative standards, biomaterial-enhanced BMC therapy may become a new option for the treatment of MI.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was funded by the Natural Sciences and Engineering Research Council of Canada (Discovery Grant #342107) and by the Ontario Research Excellence Fund (SCORR #RE07-086). B Nadlacki was supported by an Ontario Graduate Scholarship Award.