I was inspired for writing this summary after attending of the International Society for Cellular Therapy annual meeting and great talks by pioneers of clinical tissue engineering – Anthony Atala and Paolo Macchiarini.
Tissue engineering is a clinical reality today. Anthony Atala has clinical data for implantation of tissue engineered bladder – 10 years outcome, vagina and urethra – 6 years outcome. Moreover, tissue engineering is successfully commercialized branch of regenerative medicine:
It is therefore highly interesting to note a comment from Geoff MacKay, CEO and President of Organogenesis that, “In the USA, on average, once every 2 minutes Monday to Friday a patient is treated with Apligraf.â€
So, what is the current status and trends in developing new tissue engineering methodologies? I’ll indicate a few most promising directions below:
1. Bionic tissue engineered construct fabrication versus bioreactor
Paolo Macchiarini, who performed the first first adult stem cell grown tissue-engineered trachea transplant, reported about new clinical approach which he started to use – bionic tissue engineering. Technology relies on using our own body as a bioreactor.
Firstly, it allows better vascularization and innervation of transplant. Secondly, this approach allows to avoid long-term cell culture step in tissue engineered construct fabrication and makes whole process easier, less time consuming and less costly. Macchiarini used freshly isolated bone marrow cells and growth factors embedded in decellularized biomatrix. After implantation, this composition caused migration of patient’s own cells. He reported first clinical case of engineered bionic trachea implantation.
2. Bioprinting
Bioprinting is an automated (by printer) programmed 3D cell seeding on the scaffold. This is a self-assembly based approach. It has advantages compared to manual cell stratification. Last year the first commercially available printer was made by Organovo. I can’t wait when first bioprinted organ will be implanted into human.
3. Scaffolds with a growth factors – cell therapy in situ
In situ bioreactive devices contain:
…appropriate combinations of scaffold composition, architecture, growth factors, proteins, and adhesion molecules can be used to obtain complex control over a variety of cell and tissue types.
Once implanted, this device cause mobilization of your own (mostly bone marrow) cells and modulation their activity depends on body’s needs. By changing growth factors composition embedded in the scaffold you can play with different subsets of bone marrow and blood cells. The concept was developed by Davind Mooney and commercialized by InCytu.
Some examples:
- * PLG matrix with mobilized GM-CSF and tumor antigen. G-CSF attracts dendritic cells, which start to expand and present tumor antigen. After release, antigen-presenting dendritic cells migrate to lymphoid organs and activate specific anti-tumor clon of cytotoxic T-cells.
* Alginate scaffold with VEGF and endothelial progenitors. VEGF could attract endogenous endothelial cells or support scaffold-embed ones and stimulate local neovascularization.
4. Decellularized biomatrix versus polymer scaffold
Antony Atala and Paolo Macchiarini both noted huge clinical potential of using decellularized cadaver organs as a matrix for tissue engineering. Macchiarini was the first who actually implanted such construct into the patient.
More about technique you can learn from Doris Taylor – who introduced this approach for fabrication of the heart.
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