Placental mesenchymal stem cell sheets: motivation for bio-MEMS device to create patient matched myocardial patches
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Congenital heart defects are the number one cause of birth defect-related deaths. Cardiovascular diseases are the most common cause of death worldwide. Layered cellular sheet constructs offer one very valuable option for cardiac patch implantation during surgical treatment of both pediatric and adult patients with cardiac defects or damage. A very exciting, relatively unexplored, autologous, available cell source for making patches are placenta-derived mesenchymal stem cells (pMSCs). In this study, pMSCs were assessed as a potential cell source for cardiac repair and regeneration by evaluating their differentiation capacity into cardiomyocytes, their effects on cardiac cell migration and proliferation, and their ability to be grown into cell sheets. It was found that pMSC cardiac protein content was enhanced by differentiation media treatment, but no beating cells were produced. Undifferentiated pMSCs improved migration and proliferation of a cardiac cell population and formed intact, aligned cell sheets. However, like many new cell sources for cardiac repair, pMSCs should still be functionally characterized to understand how compatible they will be with resident heart tissue. Implanting non-autologous, potentially pluripotent, non-myocyte (non-beating) cells presents concerns regarding electromechanical mismatch and implant rejection. The characterization of non-traditional cell sources such as pMSCs motivated the design of a bio-MEMS device that assesses contractile force and conduction velocity in response to electrical and mechanical stimulation of a cell source as it is grown and once it forms a cellular sheet. This ideally creates the ability for patient specific cell sheets to be cultured, characterized, and conditioned to be compatible with the patient’s cardiac environment in vitro, prior to implantation. In this work, the device was designed to achieve the following: cellular alignment, electrical stimulation, mechanical stimulation, conduction velocity readout, contraction force readout, and upon characterization, cell sheet release. The platform is based on a set of comb electrical contacts which are three dimensional wall contacts made of polydimethylsiloxane and coated with electrically conductive metals. Device fabrication and initial validation experiments were completed as part of this study; ultimately the device will allow for the complete functional characterization and conditioning of variable cell source cell sheet implants for myocardial implantation.
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