The main topics of the conference included: human iPS cells with emphasis on the clinical applications, tissue engineering and regenerative medicine. The first session of the meeting was chaired by Dr.
|Scooped by Christopher Duntsch|
This is a good review and report of what is trending now in tissue engineering. The push early was therapies with cells derived from mature tissue, or tissue sections from mature tissues, that were transferred into a degenerated, damaged, or diseased tissue with the hope of some sort of therapeutic or regenerative healing or reversal of the disease process. There are a few exceptions, but this approach never worked well in vitro, in vivo in animals, much less in the clinical studies that followed. The shift to stem cell technologies was a paradigm shift and in the right direction, but still there has not been a great deal of success using stem cell therapies in isolation. There are rare exceptions as always (HSCs and BM transplants).
Years ago and even more so recently, the definition of tissue engineering, has changed significantly. There are now so called core components, and is agreed by most that the ‘sum of the parts are greater than the "whole". In the most basic sense, I would think it could be simplified to 1) a stem cell product or therapeutic 2) support factors of many types … growth factors, nutrients, supplements, etc., 3) a 3D scaffold of some type.
This article keys in on successes that have begun to be seen in the scientific literature as of late. Namely, that in addition to the above, one must consider the impact of stem cells as before, but also of progenitor cells, changes in phenotype that are smart and strategic and also in line with fundamental biology, and for lack of a better word for it, developmental biology. In any normal solid organ, there is a rare but immortal adult stem cell population, and that stem cell is quiescent most often, at least in a healthy state. However, inflammation and other molecular events that occur with disease and damage and degeneration can push quiescent stem cells to asymmetrically give off early progenitors. These are the machines of tissue development, as they are of effective regenerative medicine.
As early progenitors mature, they change in phenotype, lose stem cell phenotypy, and gain terminal lineage phenotypy. Eventually, as cells proliferate and migrate and fill a tissue niche, they crowd and mature and secrete ECM and enzymes. EC enzymes such as MMPs, and Cell surface adhesion molecules and receptors, interact with ECM such as proteoglycans and glycosaminoglycans, and eventually cells fix in space in time, communicate locally, and organize. The result is prefabricated tissue that is the infrastructure and architectural pathway to the end goal.. As this remodels continuously, the cell and tissue and the structure / architecture remodels and continues to mature and evolve. Ideally, a relatively regenerated tissue with structure, order, and function, is left where once there was damaged or nonfunctional tissue.
The point of the above is that the rough approximation of developmental biology in vitro in not just important but required for successful tissue engineering. And this requires more than the three core components mentioned. Without more detail, it is enough to simply make these descriptive comments. Despite the lack of detail for what follows, it is fairly logical to assume that an in vitro developmental biology influence is indeed a key fourth core for tissue engineering.
Principles of Tissue Engineering with the following four core components.
1 A stem cell that is a proven therapeutic for the treated condition.
2 A supportive mix of growth factors, small molecules, media, glucose, ECM, as indicated.
3 A synthetic or organic but biocompatible 3D scaffold, and;
4 A series of key steps, protocols, manipulations that provide a developmental nature or influence to the biological device prior to transplant into the animal.
In summary, a definition of an ideal tissue engineering product: A stem cell therapeutic, seeded into a tissue engineering complex in vitro, supplemented with ECM, GFs, supplements, etc, which, after methods and protocols are carried forward correctly, results in a comprehensive biological device or structure that has the following components:
1 a retained stem cell fraction with a phenotypically correct phenotype,
2 an early progenitor fraction rapidly dividing and migrating throughout the structure, and,
3 a small late progenitor fraction that is beginning to some degree to mature to the lineage of the cells needed for the tissue treated.
The importance is that the biological device used for tissue engineering is: primed genetically, epigenetically, and with respect to its cell and molecular phenotype; phenotypically more effective at integrating / assimilating into the target tissue, and immediately starts to grow, mature, change, and regenerate the tissue defect or replace / treat / supplement a diseased or degenerated tissue. Makes sense.