The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy
The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy
BMB Reports. 2014. Mar, 47(3): 135-140
Copyright © 2014, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : December 18, 2013
  • Accepted : January 13, 2014
  • Published : March 30, 2014
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About the Authors
Eun Young Kim
Laboratory of Animal Reproduction and Physiology, Department of Animal Science and Biotechnology, College of Agriculture and Life Science, Chungnam National University, Daejeon 305-764, Korea
Kyung-Bon Lee
Department of Biology Education, College of Education, Chonnam National University, Gwangju 500-757, Korea
Min Kyu Kim
Laboratory of Animal Reproduction and Physiology, Department of Animal Science and Biotechnology, College of Agriculture and Life Science, Chungnam National University, Daejeon 305-764, Korea

The mesenchymal stem cells (MSCs), which are derived from the mesoderm, are considered as a readily available source for tissue engineering. They have multipotent differentiation capacity and can be differentiated into various cell types. Many studies have demonstrated that the MSCs identified from amniotic membrane (AM-MSCs) and amniotic fluid (AF-MSCs) are shows advantages for many reasons, including the possibility of noninvasive isolation, multipotency, self-renewal, low immunogenicity, anti-inflammatory and nontumorigenicity properties, and minimal ethical problem. The AF-MSCs and AM-MSCs may be appropriate sources of mesenchymal stem cells for regenerative medicine, as an alternative to embryonic stem cells (ESCs). Recently, regenerative treatments such as tissue engineering and cell transplantation have shown potential in clinical applications for degenerative diseases. Therefore, amnion and MSCs derived from amnion can be applied to cell therapy in neuro-degeneration diseases. In this review, we will describe the potential of AM-MSCs and AF-MSCs, with particular focus on cures for neuronal degenerative diseases. [BMB Reports 2014; 47(3): 135-140]
As tissue engineering has developed, cell-based therapy has emerged in clinical trials due to potential applications in regenerative medicine. Tissue engineering using stem cells has introduced a new field of repair in the treatment of degenerative tissues or diseases.
The central nervous system (CNS), is typically an unrecoverable site, that it, it cannot be completely regenerated after damaged (1) . Therefore, most degenerative neurological diseases and mechanical and physical injuries remain incurable. To improve the treatment of neurodegenerative disorders, stem cell-based regenerative therapy has been investigated. Moreover, the various types of stem cells include embryonic stem cells (ESCs), adult stem cells, mesenchymal stem cells (MSCs), and induced pluripotent stem (iPS) cells have been considered as possible sources of regenerative treatment.
MSCs, generally from adult stem cells, are derived from the mesoderm and identified available in mammal tissues, such as bone marrow, adipose, umbilical cord blood, olfactory bulb, amnion, and Wharton’s jelly (2 , 3) . MSCs can be multipotent and differentiated into various cell types, not only mecenchymal lineage cells, such as chondrocytes, adipocytes, osteocytes, but also nonmesodermal lineage, such as epithelial cells, hepatocyte cells, cardiomyocyte cells, insulin secreting pancreatic β-cells, and neuronal cells (4 - 9) . In addition, MSCs have several advantages, including their nontumorigenicity and anti-immunogenic activity and minimal ethical problems compared with any other candidates for regenerative therapy. These facts suggest that MSCs are considered a readily available source for regenerative medicine.
The MSCs derived from amniotic membrane (AM-MSCs) and amniotic fluid (AF-MSCs) have been reported as a better new prospective field of regenerative medicine compared with other MSCs sources, because of the easily of their acquisition, reduced donor damage, multipotency, low immune response, and acceptable ethical issue (10) .
In this review, we will describe the potential of the AF-MSCs and AM-MSCs in tissue engineering and cell transplantation strategies for curing degenerative neuronal diseases.
- Embryonic stem cells (ESCs) vs. induced pluripotent stem (iPS) cells
The research on ESCs began with the establishment of mouse ESCs lines in 1981, and it advanced with the first cultivation of human ESCs derived from blastocyst in 1998 (11 , 12) . Commonly, ESCs are capable of long-term self-renewal and maintaining a continuously undifferentiated state, and they have the pluripotent differentiation ability (13) . With these characteristics, ESCs can be considered as significant biomedical materials for developmental biology and regenerative medicine.
However, despite the outstanding potential of ESCs, they still have some drawbacks for clinical use. Many experimental studies observed tumor formation after injection of ESCs for treating injury (14) . Moreover, this tumor formation with the immunogenicity lead to safety concerns, and thus the modification of ESCs of cell-based therapies has difficulties. In addition to the safety concerns involved in ESCs-based therapy, ethical concerns are another issue. The moral debate surrounding testing to discover the potential of ESCs continues.
The iPS cells are a type of pluripotent stem cell, which are artificially induced by inducing a few specific transcription factors into nonstem cells. The reprogrammed cells also differentiate into various cell types including the three major cell types, both in vivo and in vitro (15) . These established iPS cells are pluripotent stem cells, which eliminates the concern of immune rejection, and they can be used for the patient-specific transplantation therapy.
However, using the viral transfection system creates concern for clinical applications. This viral genome integration into the host genome might increase the risk for formation of teratoma (16) . In the reprogramming process, the insertion of genes randomly located in the host cell’s genome results in unstable expression of the pluripotent genes and chromosomes. Thus, a reprogramming technique for safe iPS cells should be developed for cell therapies with iPS cells.
- Amniotic-membrane-derived mesenchymal stem cells
The amniotic membrane is a component of the placenta that originates in the extra-embryonic tissue and functions to protect the fetus during pregnancy with supplemental nutrients. The amniotic membrane is generally known as bio-material for treatment scaffolds of burns, skin, and corneal transplantation, because it has the ability to scarring reduction and anti-inflammatory properties (17) . Currently, the amniotic membrane is widely used as material for clinical treatment ( Table 1 ).
Current state of therapeutic potential in amniotic membrane
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MRKH: mayer-rokitansky-küster-hauser syndrome.
The AM-MSCs can differentiate into all three germ layers for ectodermal lineage cells, mesodermal lineage cells, and endodermal lineage cells (18) . They are positively expressed mesenchymal markers, such as CD105 and CD90, and negatively expressed hematopoietic markers, such as CD29, CD34, CD45, and CD105 (19) . In addition, the amniotic membrane expresses anti-angiogenic and anti-inflammatory proteins, and does not express human leukocyte antigen (HLA)-A, -B, and DR antigens (20) . These results show that the AM-MSCs are very important for advanced regenerative medicine, because inflammatory and immunogenicity remain indispensable factors in successful transplantation.
Moreover, despite the pluripotent marker expression of AM-MSCs, such as Oct-4, Nanog, TRA-1-60, and TRA-1-81, they do not form teratoma (21) . In addition, the native amniotic membrane expresses many types of growth factors, and these growth factors reduce inflammation and prevent fibrosis induced by inflammation (22) . Further, amniotic membrane has no blood vessels or nerves, and it enhances wound healing by inhibition of proteinase activity (23) . Therefore, immunological rejection after transplantation does not occur in the amniotic membrane and the cells derived from it. For these reasons, amniotic membrane and AM-MSCs might be useful sources for transplantation for regenerative disease treatment.
- Amniotic fluid-derived mesenchymal stem cells
The amniotic fluid was formed at 2 weeks after fertilization in the amniotic cavity of early gestation. Amniotic fluid is important to keep the fetus safe, and it supports organ development. The first progenitor cells derived from amniotic fluid was reported in 1993 by Torricelli et al. (24) . The amniotic fluids incorporated a heterogeneous population of cells of fetal origin, and these cells maintained fetal-specific alleles without loss of the chromosomal telomere length in 250 doubling times (25) .
Recently, many studies have identified amniotic fluid (AF) as a new source of MSCs, and these AF-MSCs express the pluripotent marker Oct-4 in almost 90% of the active condition, and they also have multiple differentiation capacity like the AM-MSCs (26 , 27) . Further, AF is routinely used to perform the standard evaluation of karyotyping and they are genetic and molecular tested for diagnostic purposes. After prenatal diagnostic testing, AF cells can be used as a source of fetal progenitor cells or otherwise discarded (28) . Use of these cells could minimize the ethical objections, have a high renewal activity, and maintain stability. The AF-MSCs enable the uses of autologous cells obtained from patients’ tissues. They can be easily isolated. Moreover, they maintain genetic stability and offer advantages of nontumorigenicity, low immunogenic activity, and present minimal ethical issues. These findings show that AF-MSCs are being considered as potential sources of treatment by many researches and clinical application ( Table 2 ).
Clinical application of amniotic fluid
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Clinical application of amniotic fluid
- Application for neuronal regenerative therapy
Despite the inability to regenerate injured CNSs, research focused on repairing damage resulting from neurodegenerative diseases is a public interest (29) . As research continues, the clinical trials of stem cell-mediated neuronal regeneration therapy are being announced. Many of MSC-type cell studies have reported that MSCs have the ability of differentiated into neural-like cells in vitro and they have a long history as potential sources for neural differentiation studies (30 - 32) .
Recent research has confirmed that the MSCs can be remyelinated in models of demyelination that do not involved inflammation (33) . The amniotic membrane and AF have been noted as new alternative sources of MSCs that would be useful for clinical applications ( Table 3 ). In the undifferentiated condition, AM-MSC and AF-MSC membrane and amniotic fluid cells possess characteristics primed for neural differentiation by express the neuron and neurotransmitter factors (34) . Moreover, they are expressed neurotrophic factors, and these factors lead to bio delivery and enhance the protection and promote the regeneration of damaged tissue (35) .
Further, recent research has reported that dopamine and tyrosine hydroxylase (TH) enzyme weakly express undifferentiated amnion, and they are ready for use as potential sources for the induction of functional dopaminergic neurons (36) . Further, the therapeutic effects of AM-MSCs and AF-MSCs can significantly improve the motor functions of Parkinson’s diseases models (37) . Thus, amnion-derived stem cells have the potential to be differentiated into dopaminergic neurons.
From these data, we hypothesized that AM-MSCs and AF-MSCs could be attractive engraft materials of differentiation neuronal-like cells and developing cell-based treatments for various neuronal degenerative disorders.
Summary of potential property of amniotic membrane and fluid in neuronal regeneration therapy
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Summary of potential property of amniotic membrane and fluid in neuronal regeneration therapy
The limitation of the regenerative properties of the CNS is that it can be seriously life-threatening. In the world report, the number of patients with Alzheimer’s, the most common neurological disorder, is estimated at 36 million people worldwide, and Parkinson’s disease affects 1% of the population above the age of 60 (38) . A much more progressive approach of therapeutic research has suggested the possibility that stem cells may have therapeutic effects for various neurological diseases.
Stem cell-based therapeutic strategies are showing potential in experimental studies. However, some problems of stem cells including safety and ethical issues have limited their clinical use. In addition, some MSCs also have safety problems and thus clinical application of treatment is engendered. Thus, the amniotic membrane and fluid are considered as noncontroversial sources because of the use of either heterologous ESCs or the less ethically disputed MSCs.
Compared to other stem cells, amniotic cells can be easily collected during routine prenatal testing, and the amniotic membrane can also be obtained during cesarean section after birth. These isolation methods are noninvasive progress without destroying human embryos and thus alleviate the ethical controversy. A small amount of AF obtained by amniocentesis and amniotic membrane samples could produce enough MSCs for applications of tissue engineering. Further, these MSCs secrete trophic factors that may be neuro-protection and may promote nerve regeneration after being transplanted into an injured neuron or neuronal site.
As needed, AM-MSCs and AF-MSCs could be stored and provided immediately for future autologous therapy. The autologous tissues made from patient-specific cells could be applied to nonrejected transplantation. Further, studies of AM-MSCs and AF-MSCs demonstrate the prospects of potential therapeutic uses for several CNS diseases. It is hoped that these beneficial effects of AM-MSCs and AF-MSCs will gradually be develop into therapeutic outcomes for neural regeneration.
This work was supported by a grant of the “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ009333)” of the Rural Development Administration, Republic of Korea.
Ryu H. H , Lim J. H. , Byeon Y. E. , Park J. R. , Seo M. S. , Lee Y. W. , Kim W. H. , Kang K. S. , Kweon O. K. (2009) Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J. Vet. Sci. 10 273 - 284    DOI : 10.4142/jvs.2009.10.4.273
Payushina O. V. , Domaratskaya E. L. , Starostin V. I. (2006) Mesenchymal stem cells: Sources, phenotype, and differentiation potential. Biology Bulletin. 33 2 - 18    DOI : 10.1134/S106235900601002X
Choi S. A. , Choi H. S. , Kim K. J. , Lee D. S. , Lee J. H. , Park J. Y. , Kim E. Y. , Li X. , Oh H. Y. , Lee D. S. , Kim M. K. (2013) Isolation of canine mesenchymal stem cells from amniotic fluid and differentiation into hepatocyte-like cells. In. Vitro. Cell Dev. Biol. Anim. 49 42 - 51    DOI : 10.1007/s11626-012-9569-x
Barzilay R. , Kan I. , Ben-Zur T. , Bulvik S. , Melamed E. , Offen D. (2008) Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols. Stem Cells and Development 17 547 - 554    DOI : 10.1089/scd.2007.0172
Carraro G. , Perin L. , Sedrakyan S. , Giuliani S. , Tiozzo C. , Lee J. , Turcatel G. , De Langhe S. P. , Driscoll B. , Bellusci S. , Minoo P. , Atala A. , De Filippo R. E. , Warburton D. (2008) Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages. Stem. Cells 26 2902 - 2911    DOI : 10.1634/stemcells.2008-0090
Connell J. P. , Camci-Unal G. , Khademhosseini A. , Jacot J. G. (2013) Amniotic Fluid-Derived Stem Cells for Cardiovascular Tissue Engineering Applications. Tissue Engineering Part B-Reviews. 19 368 - 379    DOI : 10.1089/ten.teb.2012.0561
Sun N. Z. , Ji H. S. (2009) In vitro differentiation of human placenta-derived adherent cells into insulin-producing cells. J. Int. Med. Res. 37 400 - 406    DOI : 10.1177/147323000903700215
Moussavou G. , Kwak D. H. , Lim M. U. , Kim J. S. , Kim S. U. , Chang K. T. , Choo Y. K. (2013) Role of gangliosides in the differentiation of human mesenchymal-derived stem cells into osteoblasts and neuronal cells. BMB Rep. 46 527 - 532    DOI : 10.5483/BMBRep.2013.46.11.179
Li R. D. , Deng Z. L. , Hu N. , Liang X. , Liu B. , Luo J. , Chen L. , Yin L. , Luo X. , Shui W. , He T. C. , Huang W. (2012) Biphasic effects of TGFbeta1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells. BMB Rep. 45 509 - 514    DOI : 10.5483/BMBRep.2012.45.9.053
Toda A. , Okabe M. , Yoshida T. , Nikaido T. (2007) The potential of amniotic membrane/amnion-derived cells for regeneration of various tissues. J. Pharmacol. Sci. 105 215 - 228    DOI : 10.1254/jphs.CR0070034
Evans M. J. , Kaufman M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292 154 - 156    DOI : 10.1038/292154a0
Thomson J. A. , Itskovitz-Eldor J. , Shapiro S. S. , Waknitz M. A. , Swiergiel J. J. , Marshall V. S. , Jones J. M. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282 1145 - 1147    DOI : 10.1126/science.282.5391.1145
Amit M. , Margulets V. , Segev H. , Shariki K. , Laevsky I. , Coleman R. , Itskovitz-Eldor J. (2003) Human feeder layers for human embryonic stem cells. Biol. Reprod. 68 2150 - 2156    DOI : 10.1095/biolreprod.102.012583
Seminatore C. , Polentes J. , Ellman D. , Kozubenko N. , Itier V. , Tine S. , Tritschler L. , Brenot M. , Guidou E. , Blondeau J. , Lhuillier M. , Bugi A. , Aubry L. , Jendelova P. , Sykova E. , Perrier A. L. , Finsen B. , Onteniente B. (2010) The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors. Stroke 41 153 - 159    DOI : 10.1161/STROKEAHA.109.563015
Abad M. , Mosteiro L. , Pantoja C. , Canamero M. , Rayon T. , Ors I. , Grana O. , Megias D. , Dominguez O. , Martinez D. , Manzanares M. , Ortega S. , Serrano M. (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502 340 - 345    DOI : 10.1038/nature12586
Medvedev S. P. , Shevchenko A. I. , Zakian S. M. (2010) Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine. Acta. Naturae 2 18 - 28
Dua H. S. , Azuara-Blanco A. (1999) Amniotic membrane transplantation. Br. J. Ophthalmol. 83 748 - 752    DOI : 10.1136/bjo.83.6.748
Tamagawa T. , Oi S. , Ishiwata I. , Ishikawa H. , Nakamura Y. (2007) Differentiation of mesenchymal cells derived from human amniotic membranes into hepatocyte-like cells in vitro. Hum. Cell 20 77 - 84    DOI : 10.1111/j.1749-0774.2007.00032.x
in't Anker P. S. , Scherjon S. A. , Kleijburg-van der Keur C. , de Groot-Swings G. M. J. S. , Claas F. H. J. , Fibbe W. E. , Kanhai H. H. H. (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22 1338 - 1345    DOI : 10.1634/stemcells.2004-0058
Adinolfi M. , Akle C. A. , McColl I. , Fensom A. H. , Tansley L. , Connolly P. , Hsi B. L. , Faulk W. P. , Travers P. , Bodmer W. F. (1982) Expression of HLA antigens, beta 2-microglobulin and enzymes by human amniotic epithelial cells. Nature 295 325 - 327    DOI : 10.1038/295325a0
Miki T. , Lehmann T. , Cai H. , Stolz D. B. , Strom S. C. (2005) Stem cell characteristics of amniotic epithelial cells. Stem Cells 23 1549 - 1559    DOI : 10.1634/stemcells.2004-0357
Tseng S. C. , Li D. Q. , Ma X. (1999) Suppression of transforming growth factor-beta isoforms, TGF-beta receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J. Cell Physiol. 179 325 - 335
Kim J. S. , Kim J. C. , Na B. K. , Jeong J. M. , Song C. Y. (2000) Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn. Exp. Eye Res. 70 329 - 337    DOI : 10.1006/exer.1999.0794
Torricelli F. , Brizzi L. , Bernabei P. A. , Gheri G. , Di Lollo S. , Nutini L. , Lisi E. , Di Tommaso M. , Cariati E. (1993) Identification of hematopoietic progenitor cells in human amniotic fluid before the 12th week of gestation. Ital. J. Anat. Embryol. 98 119 - 126
Shay J. W. , Wright W. E. (2000) Hayflick, his limit, and cellular ageing. Nat. Rev. Mol. Cell Biol. 1 72 - 76    DOI : 10.1038/35036093
Tsai M. S. , Lee J. L. , Chang Y. J. , Hwang S. M. (2004) Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum. Reprod. 19 1450 - 1456    DOI : 10.1093/humrep/deh279
De Coppi P. , Bartsch G. Jr. , Siddiqui M. M. , Xu T. , Santos C. C. , Perin L. , Mostoslavsky G. , Serre A. C. , Snyder E. Y. , Yoo J. J. , Furth M. E. , Soker S. , Atala A. (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25 100 - 106    DOI : 10.1038/nbt1274
Prusa A. R. , Hengstschlager M. (2002) Amniotic fluid cells and human stem cell research: a new connection. Med. Sci. Monit. 8 RA253 - 257
Okano H. , Ogawa Y. , Nakamura M. , Kaneko S. , Iwanami A. , Toyama Y. (2003) Transplantation of neural stem cells into the spinal cord after injury. Semin. Cell Dev. Biol. 14 191 - 198    DOI : 10.1016/S1084-9521(03)00011-9
Tropel P. , Platet N. , Platel J. C. , Noel D. , Albrieux M. , Benabid A. L. , Berger F. (2006) Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells 24 2868 - 2876    DOI : 10.1634/stemcells.2005-0636
Tio M. , Tan K. H. , Lee W. , Wang T. T. , Udolph G. (2010) Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells. PLoS One 5 e9398 -    DOI : 10.1371/journal.pone.0009398
Kim E. Y. , Lee K. B. , Yu J. , Lee J. H. , Kim K. J. , Han K. W. , Park K. S. , Lee D. S. , Kim M. K. (2013) Neuronal cell differentiation of mesenchymal stem cells originating from canine amniotic fluid. Hum. Cell 2013 Oct 29. [Epub ahead of print]
Tremblay R. G. , Sikorska M. , Sandhu J. K. , Lanthier P. , Ribecco-Lutkiewicz M. , Bani-Yaghoub M. (2010) Differentiation of mouse Neuro 2A cells into dopamine neurons. J. Neurosci. Methods 186 60 - 67    DOI : 10.1016/j.jneumeth.2009.11.004
Uchida S. , Inanaga Y. , Kobayashi M. , Hurukawa S. , Araie M. , Sakuragawa N. (2000) Neurotrophic function of conditioned medium from human amniotic epithelial cells. J. Neurosci. Res. 62 585 - 590
Pan H. C. , Yang D. Y. , Chiu Y. T. , Lai S. Z. , Wang Y. C. , Chang M. H. , Cheng F. C. (2006) Enhanced regeneration in injured sciatic nerve by human amniotic mesenchymal stem cell. J. Clin. Neurosci. 13 570 - 575    DOI : 10.1016/j.jocn.2005.06.007
Kakishita K. , Elwan M. A. , Nakao N. , Itakura T. , Sakuragawa N. (2000) Human amniotic epithelial cells produce dopamine and survive after implantation into the striatum of a rat model of Parkinson's disease: A potential source of donor for transplantation therapy. Experimental Neurology 165 27 - 34    DOI : 10.1006/exnr.2000.7449
Portmann-Lanz C. B. , Schoeberlein A. , Huber A. , Sager R. , Malek A. , Holzgreve W. , Surbek D. V. (2006) Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am. J. Obstet. Gynecol. 194 664 - 673    DOI : 10.1016/j.ajog.2006.01.101
Ariga H. , Takahashi-Niki K. , Kato I. , Maita H. , Niki T. , Iguchi-Ariga S. M. (2013) Neuroprotective function of DJ-1 in Parkinson's disease. Oxid. Med. Cell Longev. 2013 683920 -    DOI : 10.1155/2013/683920
Tseng S. C. , Di Pascuale M. A. , Liu D. T. , Gao Y. Y. , Baradaran-Rafii A. (2005) Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases. Ophthalmology 112 896 - 903    DOI : 10.1016/j.ophtha.2004.11.041
Mohammadi A. A. , Johari H. G. , Eskandari S. (2013) Effect of amniotic membrane on graft take in extremity burns. Burns 39 1137 - 1141    DOI : 10.1016/j.burns.2013.01.017
Khademi B. , Bahranifard H. , Azarpira N. , Behboodi E. (2013) Clinical application of amniotic membrane as a biologic dressing in oral cavity and pharyngeal defects after tumor resection. Arch. Iran. Med. 16 503 - 506
Samandari M. H. , Yaghmaei M. , Ejlali M. , Moshref M. , Saffar A. S. (2004) Use of amnion as a graft material in vestibuloplasty: a preliminary report. Oral. Surg. Oral. Med. Oral. Pathol. Oral Radiol. Endod. 97 574 - 578    DOI : 10.1016/j.tripleo.2003.10.031
Gharib M. , Ure B. M. , Klose M. (1996) Use of amniotic grafts in the repair of gastroschisis. Pediatr. Surg. Int. 11 96 - 99    DOI : 10.1007/BF00183734
Liu Y. , Cao D. L. , Guo L. B. , Guo S. N. , Xu J. K. , Zhuang H. F. (2013) Amniotic stem cell transplantation therapy for type 1 diabetes: a case report. J. Int. Med. Res. 41 1370 - 1377    DOI : 10.1177/0300060513487640
Steigman S. A. , Ahmed A. , Shanti R. M. , Tuan R. S. , Valim C. , Fauza D. O. (2009) Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells. J. Pediatr. Surg. 44 1120 - 1126    DOI : 10.1016/j.jpedsurg.2009.02.038
Wu Z. Y. , Hui G. Z. , Lu Y. , Wu X. , Guo L. H. (2006) Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury. Chin. Med. J. (Engl). 119 2101 - 2107
Xue H. , Zhang X. Y. , Liu J. M. , Song Y. , Li Y. F. , Chen D. (2013) Development of a chemically extracted acellular muscle scaffold seeded with amniotic epithelial cells to promote spinal cord repair. J. Biomed. Mater. Res. A. 101 145 - 156    DOI : 10.1002/jbm.a.34311
de Weerd L. , Weum S. , Sjavik K. , Acharya G. , Hennig R. O. (2013) A new approach in the repair of a myelomeningocele using amnion and a sensate perforator flap. J. Plast. Reconstr. Aesthet. Surg. 66 860 - 863    DOI : 10.1016/j.bjps.2012.11.020
McCarthy S. , Sarwar M. , Virapongse C. , Ehrenkranz R. (1984) Craniofacial anomalies in the amniotic band disruption complex. Pediatr. Radiol. 14 44 - 46    DOI : 10.1007/BF02386731
Doret M. , Cartier R. , Miribel J. , Massardier J. , Massoud M. , Bordes A. , Moret S. , Gaucherand P. (2013) Premature preterm rupture of the membrane diagnosis in early pregnancy: PAMG-1 and IGFBP-1 detection in amniotic fluid with biochemical tests. Clin. Biochem. 46 1816 - 1819    DOI : 10.1016/j.clinbiochem.2013.10.006
Skardal A. , Mack D. , Kapetanovic E. , Atala A. , Jackson J. D. , Yoo J. , Soker S. (2012) Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl. Med. 1 792 - 802    DOI : 10.5966/sctm.2012-0088
Weber B. , Emmert M. Y. , Behr L. , Schoenauer R. , Brokopp C. , Drogemuller C. , Modregger P. , Stampanoni M. , Vats D. , Rudin M. , Burzle W. , Farine M. , Mazza E. , Frauenfelder T. , Zannettino A. C. , Zund G. , Kretschmar O. , Falk V. , Hoerstrup S. P. (2012) Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation. Biomaterials 33 4031 - 4043    DOI : 10.1016/j.biomaterials.2011.11.087
Villani V. , Milanesi A. , Sedrakyan S. , Da Sacco S. , Angelow S. , Conconi M. T. , Di Liddo R. , De Filippo R. , Perin L. (2014) Amniotic fluid stem cells prevent beta-cell injury. Cytotherapy 16 41 - 55    DOI : 10.1016/j.jcyt.2013.08.010
Tajiri N. , Acosta S. , Glover L. E. , Bickford P. C. , Jacotte Simancas A. , Yasuhara T. , Date I. , Solomita M. A. , Antonucci I. , Stuppia L. , Kaneko Y. , Borlongan C. V. (2012) Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats. PLoS One 7 e43779 -    DOI : 10.1371/journal.pone.0043779
Liu Y. W. , Roan J. N. , Wang S. P. , Hwang S. M. , Tsai M. S. , Chen J. H. , Hsieh P. C. (2013) Xenografted human amniotic fluid-derived stem cell as a cell source in therapeutic angiogenesis. Int. J. Cardiol. 168 66 - 75    DOI : 10.1016/j.ijcard.2012.09.072
Werber B. , Martin E. (2013) A prospective study of 20 foot and ankle wounds treated with cryopreserved amniotic membrane and fluid allograft. J. Foot Ankle Surg. 52 615 - 621    DOI : 10.1053/j.jfas.2013.03.024
Tsai M. S. , Hwang S. M. , Tsai Y. L. , Cheng F. C. , Lee J. L. , Chang Y. J. (2006) Clonal amniotic fluid-derived stem cells express characteristics of both mesenchymal and neural stem cells. Biol. Reprod. 74 545 - 551    DOI : 10.1095/biolreprod.105.046029
McLaughlin D. , Tsirimonaki E. , Vallianatos G. , Sakellaridis N. , Chatzistamatiou T. , Stavropoulos-Gioka C. , Tsezou A. , Messinis I. , Mangoura D. (2006) Stable expression of a neuronal dopaminergic progenitor phenotype in cell lines derived from human amniotic fluid cells. J. Neurosci. Res. 83 1190 - 1200    DOI : 10.1002/jnr.20828
Xue S. , Chen C. , Dong W. , Hui G. , Liu T. , Guo L. (2012) Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1DeltaE9-deleted genes. Sci. China Life Sci. 55 132 - 140    DOI : 10.1007/s11427-012-4283-1
Chang Y. J. , Ho T. Y. , Wu M. L. , Hwang S. M. , Chiou T. W. , Tsai M. S. (2013) Amniotic fluid stem cells with low gamma-interferon response showed behavioral improvement in parkinsonism rat model. PLoS One 8 e76118 -    DOI : 10.1371/journal.pone.0076118
Pan H. C. , Chin C. S. , Yang D. Y. , Ho S. P. , Chen C. J. , Hwang S. M. , Chang M. H. , Cheng F. C. (2009) Human amniotic fluid mesenchymal stem cells in combination with hyperbaric oxygen augment peripheral nerve regeneration. Neurochem. Res. 34 1304 - 1316    DOI : 10.1007/s11064-008-9910-7
Rehni A. K. , Singh N. , Jaggi A. S. , Singh M. (2007) Amniotic fluid derived stem cells ameliorate focal cerebral ischaemia-reperfusion injury induced behavioural deficits in mice. Behav. Brain Res. 183 95 - 100    DOI : 10.1016/j.bbr.2007.05.028
Cheng F. C. , Tai M. H. , Sheu M. L. , Chen C. J. , Yang D. Y. , Su H. L. , Ho S. P. , Lai S. Z. , Pan H. C. (2010) Enhancement of regeneration with glia cell line-derived neurotrophic factor-transduced human amniotic fluid mesenchymal stem cells after sciatic nerve crush injury. J. Neurosurg. 112 868 - 879    DOI : 10.3171/2009.8.JNS09850
Sankar V. , Muthusamy R. (2003) Role of human amniotic epithelial cell transplantation in spinal cord injury repair research. Neuroscience 118 11 - 17    DOI : 10.1016/S0306-4522(02)00929-6