Recent advances in tissue engineering are nothing short of miraculous. Several different cells, tissues, and organs have been engineered in the laboratory using techniques ranging from stem cell differentiation to 3D printing. The results achieved to date give hope that even neuronal cells and tissues can be regenerated and used to repair damaged tissues in patients. Here I describe a few exciting examples of recent discoveries and technological advances that I have come across in the science literature within the last few weeks.
1. Functional Esophagi Grown On Organ Scaffolds
Esophagi grown on organ scaffolds from rat bone marrow mesenchymal stroma cells were implanted into rats without any need for immunosuppression. The engineered esophagi contain differentiated muscle cells, nerves, and blood vessels (1).
2. Human “Lungs” Grown on Organ Scaffolds
Lungs from fatal trauma victims were stripped of all tissue except for the collagen scaffolding. The scaffolds were suspended in a culture vessel containing freshly harvested human lung cells. After about 4 weeks, a new pseudo-lung had grown on the scaffold (2). The use of such tissues for human transplantation is probably at least 10 years away but this is an incredibly exciting and promising step. One article notes that several transplants using synthetic esophagi have already been performed.
3. Functional Bioengineered Vaginas
Four female patients have been transplanted with bioengineered vaginas grown from a small sample of the patients’ vulvar muscle and lining cells. The engineered vaginas appear to be fully functional sexually and could potentially support pregnancy (3).
4. Self-Repairing Muscle Fibers
Muscle fibers grown in the lab at Duke University and implanted into a mouse were able to become vascularized, and showed remarkable strength, contractility, and the ability to repair themselves when exposed to snake venom (4,5).
5. Engineered Red Blood Cells (RBCs)
Joanne Mountford, University of Glasgow, and Marc Turner, Scottish National Blood Transfusion Service (SNBTS) and their colleagues have generated functional human RBCs from induced pluripotent stem cells (iPSCs). Fibroblasts were differentiated or reprogrammed into induced pluripotent stem cells (iPSCs). The iPSCs were cultured in bone marrow-like conditions for about a month before the new RBCs were harvested from the cultures. The RBCs produced were type O-, the universal donor type. RBCs produced in this way are also free of pathogenic contamination. The question remains: can the process be scaled up adequately to significantly increase the supply of blood cells available for transfusion? Clinical trials are anticipated in late 2016 (6,7,8).
6. Cochlear Implants That Deliver Gene Therapy
Cochlear implants have successfully restored hearing in numerous individuals with severe hearing loss. Recently it was shown that combining cochlear implants with a form of gene therapy can improve the efficacy of cochlear implants by stimulating regenerative nerve growth within the cochlea (9,10).
7. Human Embryonic Stem Cells from Adult Skin Cells
The ability to generate human embryonic stem (ES) cells from adult skin cells raises the possibility of growing tissues and organs for individual donors. The ES cells are produced using Somatic Cell Nuclear Transfer (SCNT). An enucleated egg cell is fused with a somatic cell from the individual to be cloned, e.g. an adult. The fused egg cell is then given a signal to start dividing. If the procedure is successful an embryo will develop. This technique has been used to clone other animals, including Dolly the sheep (11).
8. Mini-Guts and Mini-Brains
Mini-guts and mini-brains have already been developed in the laboratory from human embryonic stem cells or iPSCs. After a few weeks of growing in a bioreactor miniature organoids can be observed. Recently scientists in Austria used this method to generate cerebral organoids or mini-brains in which tissue layers representing forebrain, midbrain, and hindbrain, as well as a subventricular zone, and pigmented cells indicative of early eye development were observed (12,13).
9. 3-D Printing Of Human Tissues
3-D printing of human tissues and organs using “bio ink” containing cells and growth matrix material has been developed by several groups. In one case a 3-D printed bronchial implant was used save the life of a baby with a life-threatening genetic defect. A company, Organovo, is developing 3-D tissues that can be used for in vitro drug screening (14,15,16).
What I have reported here are just a few examples of tissue engineering and tissue generation that have appeared in the news recently. Together these discoveries lay the groundwork for a future in which engineered cells, tissues, and entire organs, grown in the laboratory, will be used routinely to replace or repair damaged tissues without the danger of rejection or immunological complications. █
- Vence T. 2014. Rats receive lab-grown esophagi: Researchers successfully transplant engineered esophagi into living rats. The Scientist Magazine Online. April 16, 2014. http://www.the-scientist.com/?articles.view/articleNo/39719/title/Rats-Receive-Lab-Grown-Esophagi/.
- Cohen E. 2014. Human lung made in lab for first time. CNN Online. February 14, 2014. http://www.cnn.com/2014/02/14/health/texas-lungs-grown/.
- Akst J. 2014. Women receive lab-grown vaginas: Doctors implant custom-made organs, built from a tissue sample and a biodegradable scaffold, into four female patients born with underdeveloped or missing vaginas. The Scientist Magazine Online, April 14, 2014. http://www.the-scientist.com/?articles.view/articleNo/39696/title/Women-Receive-Lab-Grown-Vaginas/.
- Franco M. 2014. Lab-made muscle repairs itself in supermouse: Duke University researchers create living skeletal muscle that looks and acts very much like the real thing — even down to repairing itself. Then they attack it. Cnet Sci-Tech Online. April 3, 2014. http://www.cnet.com/news/lab-made-muscle-repairs-itself-in-mouse/
- Juhas M, Engelmayr GC Jr, Fontanella AN, Palmer GM, and Bursac N. 2014. Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo. Proc Natl Acad Sci U S A. 111(15): 5508-13. http://www.pnas.org/content/111/15/5508.abstract.
- Akst J. 2014. Artificial blood is patient-ready: In the midst of news that engineered organs are being implanted into animals and people, researchers announce the creation of artificial blood for transplant. The Scientist Magazine Online. April 16, 2014. http://www.the-scientist.com/?articles.view/articleNo/39718/title/Artificial-Blood-Is-Patient-Ready/.
- Franco M. 2014. Lab grows blood for human trials: Human volunteers in the near future will test out blood created from engineered stem cells. Someday facilities could make type O on demand, like real-life Tru Blood factories. Cnet Sci-Tech Online. April 15, 2014. http://www.cnet.com/news/lab-grows-blood-for-human-trials-like-real-life-tru-blood/.
- Stem Cells For Blood Transfusion. http://www.stemcellsforblood.org/contact.htm.
- Pinyon JL, Tadros SF, Froud KE, Wong ACY, Tompson IT, Crawford EN, Ko M, Morris R, Klugmann M, and Housley GD. 2014. Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Sci. Transl. Med. 6, 233ra54. http://stm.sciencemag.org/content/6/233/233ra54.
- Kaiser J. 2014. Implant injects DNA into ear, improves hearing. Science Now, Online 23 April 2014. http://news.sciencemag.org/brain-behavior/2014/04/implant-injects-dna-ear-improves-hearing.
- Shaikh-Lesko R. 2014. Adult-to-Stem Cells: An international team has created human embryonic stem cells from adult skin cells for the first time. The Scientist Magazine Online. April 21, 2014http://www.the-scientist.com/?articles.view/articleNo/39753/title/Adult-to-Stem-Cells/.
- Gallagher J. 2013. Miniature ‘human brain’ grown in lab. BBC News Online. 28 August 2013. http://www.bbc.com/news/health-23870462.
- Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Matthew E. Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501(7467): 373-9. http://www.nature.com/nature/journal/v501/n7467/full/nature12517.html.
- Smith S. 2013. 3-D printer helps save dying baby. CNN Online. May 23, 2013. http://www.cnn.com/2013/05/22/health/baby-surgery/index.html.
- Ferber D. 2014. An essential step toward printing living tissues: New method enables engineers to print tissue constructs with blood vessels. A new bioprinting method developed at the Harvard School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University. News & Events. February 19, 2014. http://www.seas.harvard.edu/news/2014/02/essential-step-toward-printing-living-tissues.
- Organovo Holdings, Inc. http://www.organovo.com/science-technology/bioprinting-process.
Martin I, Simmons PJ, and Williams DF. 2014. Manufacturing Challenges in Regenerative Medicine. Sci. Transl. Med. 6, 232fs16. http://stm.sciencemag.org/content/6/232/232fs16.short.
Tabar V and Studer L. 2014. Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet. 15(2): 82-92. http://www.nature.com/nrg/journal/v15/n2/full/nrg3563.html.