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Amniotic Fluid Cells for Future Tissue Engineering
Amniotic fluid has been used for more than 70 years for prenatal diagnosis (1). It is extracted, by a procedure called "amniocentesis", generally between the 14th and 20th weeks of pregnancy, to assess for genetic birth defects. In addition to the fluid required for testing, the doctor will also withdraw a small amount (a few milliliters) of additional fluid, in case any further testing is required. That extra fluid could be used to isolate fetal stem cells from the baby, as it contains a varied population of cells that originate from the tissues of the baby's skin, respiratory, digestive and urinary tracts.
Stem cells may be one important component of "tissue engineering" to maintain or repair a functional tissue or organ. Tissue engineering has the potential to revolutionize the way we deliver healthcare and may improve the quality of life for millions in the future. One of the most important applications would be to grow life-saving organs in the laboratory to replace living or cadaveric donors used in organ transplantation. There is an extreme shortage of organs available for donation, which does not allow for treatment for a large portion of patients. The need for organs far outpaces the supply.
Stem cells from many different sources are being assessed therapeutically across over 4000 trials listed on ClinicalTrials.gov. Amniotic fluid may provide an important source of immature cells discarded by the developing baby. The primitive nature of the cell may lend itself to a large number of applications due to its plasticity. There is no need to force the cells to become pluripotent, no potential to grow tumors, and no ethical considerations associated with the cell. Furthermore the cells have demonstrated that they are capable of suppressing or altering an immune response (2).
Amniotic fluid cells can differentiate into the three embryonic germ cell layers, and thus harbor the potential to become every cell type in the human body. Here is a list of cell types that scientists have grown from amniotic fluid cells: adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages (3); epithelial lung (4), cardiomyogenic (5, 6), smooth muscle in a cryo-injured bladder (7), hematopoietic (8), hepatocyte (9) renal (10), and tendon (11), to name a few. A subpopulation of the cells in the amniotic fluid, referred to as c-kit+, can be expanded to more than 250 population doublings while maintaining normal chromosones and long telomeres.
What is even more exciting for the future of tissue engineering, is that some amniotic fluid cells seem to function as specific organ precursor cells (12). For example, one cell line seems to be progenitors of kidney cells. In pre-clinical studies they were able to protect kidneys from tubular necrosis (13).
In the future, amniotic fluid cells may be a useful reservoir of stem cells for in-utero treatment of congenital conditions that carry a heavy burden on the patient and society (12). A case in point would be spina bifida, which is currently under investigation. The amniotic fluid cells surrounding a sick baby can be harvested and grown to treat that baby. This can be done during the course of the pregnancy, and without fear of the cells being rejected since they are native to the patient.
Anthony Atala, M.D., Director of the Wake Forest Institute for Regenerative Medicine, has stated that 99% of the U.S. population could conceivably find genetic matches for tissue regeneration or engineered organs from just 100,000 unique amniotic fluid samples. The amniotic fluid cell source may be revolutionary in the field of healthcare as highly proliferative, immature cells capable of immune modulation.
- Baranov V.S., Kuznetsova T.V.. Cytogenetics of Human Embryonic Development. St. Petersburg. N-L. 2007:639-639.
- Moorefield EC, McKee EE, Solchaga L, Orlando G, Yoo JJ, Walker S, Furth ME, Bishop CE. Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response. PLoS One. 2011;6(10):e26535. Epub 2011 Oct 26.
- De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol. 2007 Jan;25(1):100-6. Epub 2007 Jan 7.
- Carraro G, Perin L, Sedrakyan S, Giuliani S, Tiozzo C, Lee J, Turcatel G, De Langhe SP, Driscoll B, Bellusci S, Minoo P, Atala A, De Filippo RE, Warburton D. Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages. Stem Cells. 2008 Nov;26(11):2902-11. Epub 2008 Aug 21.
- Bollini S, Pozzobon M, Nobles M, Riegler J, Dong X, Piccoli M, Chiavegato A, Price AN, Ghionzoli M, Cheung KK, Cabrelle A, O'Mahoney PR, Cozzi E, Sartore S, Tinker A, Lythgoe MF, De Coppi P. In vitro and in vivo cardiomyogenic differentiation of amniotic fluid stem cells. Stem Cell Rev. 2011 Jun;7(2):364-80.
- Bai J, Wang Y, Liu L, Chen J, Wang Y. Biocharacteristics of c-kit+ human amniotic fluid-derived mesenchymal stem cells and their differentiation into cardiomyocytes in vitro]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012 Feb;26(2):152-7.
- De Coppi P, Callegari A, Chiavegato A, Gasparotto L, Piccoli M, Taiani J, Pozzobon M, Boldrin L, Okabe M, Cozzi E, Atala A, Gamba P, Sartore S. Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells. J Urol. 2007 Jan;177(1):369-76.
- Ditadi A, de Coppi P, Picone O, Gautreau L, Smati R, Six E, Bonhomme D, Ezine S, Frydman R, Cavazzana-Calvo M, Andre-Schmutz I. Human and murine amniotic fluid c-Kit+Lin- cells display hematopoietic activity. Blood. 2009 Apr 23;113(17):3953-60. Epub 2009 Feb 12.
- Liu H, Liu DQ, Li BW, Guan LD, Yan ZF, Li YL, Pei XT, Yue W, Wang M, Lu YP, Peng HM, Lv Y. Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo. In Vitro Cell Dev Biol Anim. 2011 Oct;47(9):601-8. Epub 2011 Sep 22.
- Renal differentiation of amniotic fluid stem cells. Perin L, Giuliani S, Jin D, Sedrakyan S, Carraro G, Habibian R, Warburton D, Atala A, De Filippo RE. Cell Prolif. 2007 Dec;40(6):936-48.
- Fuchs JR, Kaviani A, Oh JT, LaVan D, Udagawa T, Jennings RW, Wilson JM, Fauza DO. Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes. J Pediatr Surg. 2004 Jun;39(6):834-8; discussion 834-8.
- Shaw SW, David AL, De Coppi P. Clinical applications of prenatal and postnatal therapy using stem cells retrieved from amniotic fluid. Curr Opin Obstet Gynecol. 2011 Apr;23(2):109-16.
- Perin L, Sedrakyan S, Giuliani S, Da Sacco S, Carraro G, Shiri L, Lemley KV, Rosol M, Wu S, Atala A, Warburton D, De Filippo RE.Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis. PLoS One. 2010 Feb 24;5(2):e9357.