Biomedical Engineering Reference
In-Depth Information
cardiomyocytes, and readily available on the shelf.
58
With their attributes of
ease of isolation, high expansion potential, genetic stability, reproducible
characteristics from isolate to isolate, reproducible characteristics in widely
dispersed laboratories, compatibility with tissue engineering principles and
potential to enhance repair in many vital tissues, MSCs possess the unique
advantages to become the preferred model for cellular therapeutic development.
13.4 Limitation of current cell therapy procedure
Despite its promising initial results from animal and clinical experience,
autologous MSCs implantation has created a logistic problem clinically in
patients having potential life-threatening cardiac events. Its clinical application
is logistically inconvenient and expensive. In the acute setting of MI, it is limited
by issues related to harvesting and culturing of sufficient quantity of autologous
MSCs promptly in patients with a critical medical condition. There is also
evidence that MSCs harvested from aged or cachectic patients are qualitatively
and quantitatively compromised.
59
It is, therefore, ideal if a `universal donor
cell' obtained from young and healthy donors readily available for cell therapy
can be used without rejection.
13.5 Unique immunological properties of MSCs
Adult stem cells are favored as the pluripotent autologous donor sources in cell
therapy because autologous cells will not be rejected by the recipients. In
ongoing investigations to use embryonic stem cells for tissue and organ regen-
eration, the need for therapeutic cloning is strongly championed by scientists in
spite of the political and ethical controversies, again to avoid immunological
rejection. In the rapidly advancing field of stem cell transplantation therapy for
various diseases including heart failure, it is taken for granted that these donor
stem cells will be subjected to immunological surveillance like any other fully
differentiated somatic cells. Yet, in recent years, a number of perplexing
observations to challenge this dogma have been reported. There is mounting
evidence in the literature to suggest that MSCs are immune-privileged cells.
60±62
MSCs can be detected in major histocompatibility complex (MHC) mismatched
recipients at extended time points without immunosuppression therapy,
63
indicating a lack of immune recognition and clearance. Liechty et al.
64
reported
that human MSCs could engraft into various tissue organs including myo-
cardium after intraperitoneal implantation in an immuno-competent fetal sheep.
This finding was again confirmed by Airey et al. in a human to sheep model.
65
Toma et al.
66
have shown that human mesenchymal stem cells could
differentiate into a cardiomyocytic phenotype in the adult murine heart. In a
swine model, Poh et al.
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and Makkar et al.
68
reported that allogeneic MSC
implantation in myocardium could survive without immunosuppressive therapy.
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