The Future of Cell Therapy and Tissue Engineering in Cardiovascular Disease:
General Material Designation
[Book]
Other Title Information
The New Era of Biological Therapeutics.
First Statement of Responsibility
Sepideh Heydarkhan-Hagvall
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
INTECH Open Access Publisher
Date of Publication, Distribution, etc.
2010
SUMMARY OR ABSTRACT
Text of Note
The use of living cells as a therapeutic option presents several challenges including identification of a suitable source, development of adequate derivation, maintenance and differentiation methods, and very importantly proof of safety and efficacy. One of the major issues for cardiovascular tissue engineering is determining the ideal cell type for use in regenerative therapies. Many clinical trials have used bone marrow derived mononuclear cells (BM-MNC) (Schächinger V 2006). These clinical trials have not shown any significant cardiomyocyte regeneration and the results have been mixed at best with no robust improvement in cardiac function (Coombs 2008). However, this trial and others have provided a proof of concept that intracoronary or intramyocardial transplant of autologous adult stem cells is safe with out any evidence of increased mortality in the treated patients. The next generation of clinical studies will need to demonstrate robust cardiomyocyte regeneration, definite improvement of cardiac pump function, and ultimately improved patient survival as the ultimate goal. The availability of the proposed cell type for regenerative medicine and tissue engineering in sufficient and relatively easily derivable quantities is also critical. To date, engineered tissue constructs containing adult and stem cells have exhibited problems with physical properties, maintenance of cell phenotypes and the host immune response to the engrafted construct. Ideally, the cells used for tissue engineering should have the capacity to proliferate and differentiate in vivo in a manner that can be reproducibly controlled and predicted (Atala A 2002). Due to the high number of cells that is needed for culturing, isolation and expansion require invasive procedures it remains a challenge to generate sufficient numbers of a single cell type, to assemble the needed mixture of multiple cell phenotypes, and to maintain stable phenotypes as needed (Atala A 2002). Furthermore, this process will need to be automated to mass produce sufficient amounts of cells and tissue constructs for clinical therapies on a wide scale. This discussion also highlights the ushering in of a new era of personalized medicine. One of the possibilities for cell therapies is patient-specific iPS cells generated from his/her own somatic cells to be used to treat that person. These designer iPS cells will be differentiated into the desired tissue types and transplanted in an autologous manner to avoid immune rejection. Although pluripotent hESCs or hiPS cells are non-immunogenic, they loose this characteristic as they become more differentiated with increased risk of immune mediated rejection if transplanted into a non-compatible patient. ASCs derived from patients may be a potential source to use to either differentiate into desired cells and re-transplant into the patient or develop and differentiate iPS cells that would be used in an autologous manner to ensure immunocompatibility as it has been shown that ASCs are much more easily induced into hiPS cells compared to fibroblasts (Sun N 2009).