Shan Liu, Jingli Zhou, Xuan Zhang, Yang Liu, Jin Chen, Bo Hu, Jinlin Song, and Yuanyuan Zhang
The goal of stem cell therapy is to regenerate damaged cells with healthy vital cells. A major issue seen in stem cell therapy occurs when the cells are being transferred from culture into the new host. Upon leaving the culture plate, stem cells tend to lose functionality and have a decreased life span due to over expansion in vitro. Long term culture also leads to a decrease in the stability of cellular DNA. Implantation of these cells can lead to higher rates of cellular mortality, low growth rates, and a diminished ability for differentiation and paracrine effects. Another important factor in the success of tissue regeneration is the quality of the implantation environment such as “blood supply, collagen density of tissue, and the numbers of existing endogenous stem cells.” Increasing the success rate of tissue regeneration using stem cells depends on utilizing the appropriate environments to optimize cellular life span and stimulating paracrine effects.
Strategies for Optimization
Source of MSCs
Mesenchymal stem cells, the most commonly used stem cell variation, is known for high rates of proliferation and paracrine effects. MSCs are multipotent cells with the ability to affect the body’s immune function. They come from various sources and seem to be the most successful in therapy when implanted into their original lineage and natural roles.
Optimal Cell Source for Cell Therapy
Combing somatic and stem cells showed an increase in the number of both cell types and the rate of tissue regeneration within the host.
Decreasing the length of time within culture can greatly increase a cell’s longevity. Utilizing non-induced stem cells may be beneficial in decreasing time spent in vitro.
Controlled-Release Exogenous Growth Factors
An effective method to produce successful treatments is to genetically manipulate cells “over-expressing diverse growth factors before implantation.”
Preconditioning Stem Cells
Strategies can be implemented to precondition stem cells for implantation and increase longevity, differentiation, and paracrine effects. Three strategies are commonly used; “hypoxia, growth factors, and a conditioned medium from functional cells or serum-free medium.”
Routes of Cell Administration
Stem cells are implanted using systemic or local approaches; each with their own advantages and disadvantages. Systemic injection is the most common method currently used.
Optimal Timing for Cell Therapy
Optimal timing differs with conditions; three phases have been identified in the healing process (the injury phase, repair phase, and remodeling phase).
Optimal Number of Cells for Injection
The amount of stem cells used in implantation should vary depending on organ type and tissue. An excessive number of cells has been shown to cause blockages in capillaries so optimizing cell number is important in achieving a successful treatment.
Rodents provide an apt, inexpensive host that has rapid tissue growth. They are not optimal for ureteral, bladder, or urethral reconstruction. Larger animal species are more expensive to maintain but have organs that very anatomically similar to that of humans.