Dario Fauza's research is directed at developing original, more effective ways to repair birth defects, both pre and postnatally. To that end, he has pioneered a variety of approaches. One is fetal tissue engineering, or the use of fetal cells to produce tissue to repair congenital anomalies. This concept involves the minimally invasive procurement of fetal cells, which are then employed to engineer tissue in the laboratory while pregnancy is allowed to continue, so that a newborn, or a fetus with a prenatally diagnosed birth defect can benefit from having autologous, expanded tissue readily available for surgical reconstruction, either before or after birth. Fetal cells can be obtained from the fetus, amniotic fluid, placenta, or umbilical cord blood. This concept has been applied successfully in many large animal models, for the creation of various types of fetal tissue used in the treatment of several anomalies, including congenital diaphragmatic hernia, tracheal atresia or stenosis, chest wall defects, bladder extrophy, cranial malformations and cardiac anomalies. Related projects for the treatment of additional birth defects are also ongoing. Regulatory approval of the first human application of this therapeutic concept is currently being pursued.
Another area of interest to Dr. Fauza is the treatment of spina bifida. He has first demonstrated experimentally that neural stem cells delivered to the fetus still in the womb can partially repair damaged areas of the spinal cord, which could lead to improved outcomes in the treatment of this devastating disease. He is now perfecting the methods for isolation of neural and mesenchymal stem cells, as well as of their pre and/or postnatal administration, before human trials can be pursued.
Dr. Fauza has also pioneered what he has coined Transamniotic Stem Cell Therapy (TRASCET), a novel therapeutic paradigm for the treatment of different birth defects based on the principle of harnessing/enhancing the normal biological role of select populations of stem cells that occur in the amniotic fluid for therapeutic benefit. He has discovered that amniotic fluid-derived mesenchymal stem cells (afMSCs) are central to the enhanced ability of the fetus to repair tissue damage. This germane finding was not only the first demonstration of a biological role for any amniotic cell, but has also provided validation for the use of afMSCs in regenerative strategies. Subsequently to that discovery, he has also first shown, in various animal models, that the simple intra-amniotic delivery of afMSCs in very large numbers can either elicit the repair, or significantly mitigate the effects associated with major congenital anomalies by boosting the activity that these cells normally have. This pragmatic approach, feasible as a relatively simple outpatient procedure, would be easily accessible to most pregnant women carrying a baby with a birth defect and from a very early point in gestation, thus maximizing therapeutic impact. Given the autologous use of fetal cells procured and delivered by the least invasive of methods, a plain amniocentesis, into their own native environment, this concept is ethically unobjectionable. Also here, regulatory approval of the first clinical trial is currently under review.
Research Background
Dario Fauza received an MD from the University of Sao Paulo Medical School, in Brazil, where he also received a PhD-equivalent degree and completed an internship and residencies on both general and pediatric surgery. He then moved to the United States, where he completed different clinical and research fellowships, as well as postdoctoral training, all at Boston Children's Hospital and Harvard Medical School.
He is the recipient of numerous research awards and funding grants, as well as of a Fellowship Ad Eundem (i.e. by invitation) from the Royal College of Surgeons of England, the first surgeon from his home country to receive such an honor. He has an extensive bibliography and has been awarded patents in multiple countries.
Education
Medical School
University of Sao Paulo
1985
Brazil
Internship
Hospital of Clinics of the University of Sao Paulo Medical School
1986
San Paulo
Brazil
Residency
Hospital of Clinics / Children's Hospital of the University of Sao Paulo Medical School
Morphometric, Developmental, and Anti-Inflammatory Effects of Transamniotic Stem Cell Therapy (TRASCET) on the Fetal Heart and Lungs in a Model of Intrauterine Growth Restriction. Stem Cells Dev. 2023 08; 32(15-16):484-490. View Abstract
Hematogenous Routing of Exogenous Messenger RNA Delivered Into the Amniotic Fluid. J Surg Res. 2023 09; 289:116-120. View Abstract
Fetal Secretory IgA Delivery via Transamniotic Fetal Immunotherapy (TRAFIT) in a Rodent Model. J Pediatr Surg. 2023 Oct; 58(10):2050-2053. View Abstract
Transamniotic Fetal Administration of Genetically Modified Hematopoietic Stem Cells Carrying a Human Transgene in a Syngeneic Rat Model. Stem Cells Dev. 2023 04; 32(7-8):180-184. View Abstract
Invited Commentary for Disruption of Enterohepatic Circulation of Bile Acids Ameliorates Small Bowel Resection Associated Hepatic Injury. J Pediatr Surg. 2023 06; 58(6):1079-1080. View Abstract
Fetal Alloimmune Hemolytic Anemia (AHA) as a Potential Target for Transamniotic Fetal Immunotherapy (TRAFIT). J Pediatr Surg. 2023 Jun; 58(6):1107-1110. View Abstract
Transamniotic stem cell therapy (TRASCET) for intrauterine growth restriction (IUGR): A comparison between placental and amniotic fluid donor mesenchymal stem cells. J Pediatr Surg. 2023 Feb; 58(2):305-309. View Abstract
Brain protection by transamniotic stem cell therapy (TRASCET) in a model of intrauterine growth restriction (IUGR). J Pediatr Surg. 2023 Jan; 58(1):3-7. View Abstract
Early functional analysis on the pulmonary hemodynamic effects of Transamniotic Stem Cell Therapy (TRASCET) in the nitrofen model of congenital diaphragmatic hernia. J Pediatr Surg. 2023 Jan; 58(1):8-13. View Abstract
Routing kinetics of human immunoglobulin-G after transamniotic fetal immunotherapy (TRAFIT) in a rodent model. J Pediatr Surg. 2022 Jun; 57(6):1004-1007. View Abstract
Intrauterine Growth Restriction (IUGR) as a potential target for transamniotic stem cell therapy. J Pediatr Surg. 2022 Jun; 57(6):999-1003. View Abstract
Routing pathway of syngeneic donor hematopoietic stem cells after simple intra-amniotic delivery. J Pediatr Surg. 2022 Jun; 57(6):986-990. View Abstract
Wound healing potential of human umbilical cord mesenchymal stem cell conditioned medium: An in vitro and in vivo study in diabetes-induced rats. Vet World. 2021 Aug; 14(8):2109-2117. View Abstract
Unselected CD117 expression in amniotic and placental mesenchymal stem cells. J Pediatr Surg. 2021 Dec; 56(12):2410-2411. View Abstract
Transamniotic Stem Cell Therapy for Experimental Congenital Diaphragmatic Hernia: Structural, Transcriptional, and Cell Kinetics Analyses in the Nitrofen Model. Fetal Diagn Ther. 2021; 48(5):381-391. View Abstract
Enhancement of transamniotic stem cell therapy for spina bifida by genetic engineering of donor mesenchymal stem cells with an Fgf2 transgene. J Pediatr Surg. 2021 Jun; 56(6):1226-1232. View Abstract
Fetal hematogenous routing of a donor hematopoietic stem cell line in a healthy syngeneic model of transamniotic stem cell therapy. J Pediatr Surg. 2021 Jun; 56(6):1233-1236. View Abstract
A novel two-component, expandable bioadhesive for exposed defect coverage: Applicability to prenatal procedures. J Pediatr Surg. 2021 Jan; 56(1):165-169. View Abstract
Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity. Fetal Diagn Ther. 2020; 47(12):902-911. View Abstract
Donor mesenchymal stem cell kinetics after transamniotic stem cell therapy (TRASCET) in a rodent model of gastroschisis. J Pediatr Surg. 2020 Mar; 55(3):482-485. View Abstract
Congenital diaphragmatic hernia as a potential target for transamniotic stem cell therapy. J Pediatr Surg. 2020 Feb; 55(2):249-252. View Abstract
A comparison between placental and amniotic mesenchymal stem cells in transamniotic stem cell therapy for experimental gastroschisis. J Pediatr Surg. 2020 Jan; 55(1):49-53. View Abstract
An experimental study on magnetic esophageal compression anastomosis in piglets. J Pediatr Surg. 2020 Mar; 55(3):425-432. View Abstract
Transamniotic stem cell therapy (TRASCET) in a rabbit model of spina bifida. J Pediatr Surg. 2019 Feb; 54(2):293-296. View Abstract
A comparison of clinically relevant sources of mesenchymal stem cell-derived exosomes: Bone marrow and amniotic fluid. J Pediatr Surg. 2019 Jan; 54(1):86-90. View Abstract
Extraluminal helicoidal stretch (Helixtretch): a novel method of intestinal lengthening. J Pediatr Surg. 2014 Dec; 49(12):1787-90. View Abstract
The impact of gestational age on targeted amniotic cell profiling in experimental neural tube defects. Fetal Diagn Ther. 2015; 37(1):65-9. View Abstract
A comparative analysis of human mesenchymal stem cell response to hypoxia in vitro: Implications to translational strategies. J Pediatr Surg. 2014 Jun; 49(6):915-8. View Abstract
Targeted quantitative amniotic cell profiling: a potential diagnostic tool in the prenatal management of neural tube defects. J Pediatr Surg. 2013 Jun; 48(6):1205-10. View Abstract
Intra-amniotic delivery of amniotic-derived neural stem cells in a syngeneic model of spina bifida. Fetal Diagn Ther. 2013; 34(1):38-43. View Abstract
Pediatric postoperative intussusception in the minimally invasive surgery era: a 13-year, single center experience. J Am Coll Surg. 2013 Jun; 216(6):1089-93. View Abstract
The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects. Stem Cells Dev. 2013 Feb 15; 22(4):548-53. View Abstract
Prenatal tracheal reconstruction with a hybrid amniotic mesenchymal stem cells-engineered construct derived from decellularized airway. J Pediatr Surg. 2012 Jun; 47(6):1072-9. View Abstract
Craniofacial repair with fetal bone grafts engineered from amniotic mesenchymal stem cells. J Surg Res. 2012 Dec; 178(2):785-90. View Abstract
Preclinical regulatory validation of an engineered diaphragmatic tendon made with amniotic mesenchymal stem cells. J Pediatr Surg. 2011 Jan; 46(1):57-61. View Abstract
Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios. J Pediatr Surg. 2011 Jan; 46(1):67-71. View Abstract
Amniotic and placental mesenchymal stem cell isolation and culture. Methods Mol Biol. 2011; 698:75-88. View Abstract
Structural and biomechanical characteristics of the diaphragmatic tendon in infancy and childhood: an initial analysis. J Pediatr Surg. 2010 Jul; 45(7):1455-8. View Abstract
Correlation between prenatal urinary matrix metalloproteinase activity and the degree of kidney damage in a large animal model of congenital obstructive uropathy. J Pediatr Surg. 2010 Jun; 45(6):1120-5. View Abstract
Chest wall repair with engineered fetal bone grafts: an efficacy analysis in an autologous leporine model. J Pediatr Surg. 2010 Jun; 45(6):1354-60. View Abstract
A large animal model of the fetal tracheal stenosis/atresia spectrum. J Surg Res. 2011 Nov; 171(1):164-9. View Abstract
Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy. J Pediatr Surg. 2010 Jan; 45(1):70-3. View Abstract
Optical properties of human amniotic fluid: implications for videofetoscopic surgery. Fetal Diagn Ther. 2010; 27(2):87-90. View Abstract
Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells. J Pediatr Surg. 2009 Jun; 44(6):1120-6; discussion 1126. View Abstract
Differential risk for neonatal surgical airway intervention in prenatally diagnosed neck masses. J Pediatr Surg. 2009 Jan; 44(1):76-9. View Abstract
Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome. J Pediatr Surg. 2009 Jan; 44(1):229-35; discussion 235. View Abstract
Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida. Surgery. 2008 Sep; 144(3):367-73. View Abstract
Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol. J Pediatr Surg. 2008 Jun; 43(6):1164-9. View Abstract
Extracorporeal membrane oxygenation as a bridge to definitive tracheal reconstruction in neonates. J Pediatr Surg. 2008 May; 43(5):800-4. View Abstract
Liver position is a prenatal predictive factor of prosthetic repair in congenital diaphragmatic hernia. Fetal Diagn Ther. 2008; 23(4):258-62. View Abstract
Autologous Approaches to Tissue Engineering. StemBook. 2008. View Abstract
A comparative analysis of cartilage engineered from different perinatal mesenchymal progenitor cells. Tissue Eng. 2007 Nov; 13(11):2633-44. View Abstract
Tissue engineering from human mesenchymal amniocytes: a prelude to clinical trials. J Pediatr Surg. 2007 Jun; 42(6):974-9; discussion 979-80. View Abstract
Isolation of mesenchymal stem cells from amniotic fluid and placenta. Curr Protoc Stem Cell Biol. 2007 Jun; Chapter 1:Unit 1E.2. View Abstract
Large fetal congenital cystic adenomatoid malformations: growth trends and patient survival. J Pediatr Surg. 2007 Feb; 42(2):404-10. View Abstract
Ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation for fetal thoracic masses. J Pediatr Surg. 2007 Feb; 42(2):420-5. View Abstract
Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia. J Pediatr Surg. 2007 Jan; 42(1):98-104; discussion 104-6. View Abstract
Percent predicted lung volumes as measured on fetal magnetic resonance imaging: a useful biometric parameter for risk stratification in congenital diaphragmatic hernia. J Pediatr Surg. 2007 Jan; 42(1):193-7. View Abstract
The second STEP: the feasibility of repeat serial transverse enteroplasty. J Pediatr Surg. 2006 Dec; 41(12):1951-6. View Abstract
Fetal hepatic haematopoiesis is modulated by arterial blood flow to the liver. Br J Haematol. 2006 Aug; 134(3):330-2. View Abstract
Pneumonectomy in the mouse: technique and perioperative management. J Invest Surg. 2005 Jul-Aug; 18(4):201-5. View Abstract
An injectable tissue-engineered embolus prevents luminal recanalization after vascular sclerotherapy. J Pediatr Surg. 2005 Jun; 40(6):920-5. View Abstract
Enhancement of intravascular sclerotherapy by tissue engineering: short-term results. J Pediatr Surg. 2005 Feb; 40(2):412-7. View Abstract
Intratracheal pulmonary ventilation improves gas exchange during laparoscopy in a pediatric lung injury model. J Pediatr Surg. 2005 Jan; 40(1):22-5. View Abstract
Amniotic fluid and placental stem cells. Best Pract Res Clin Obstet Gynaecol. 2004 Dec; 18(6):877-91. View Abstract
In situ inhibition of uterine activity by indomethacin: possible relevance to preterm labor prevention after fetal surgery. J Pediatr Surg. 2004 Aug; 39(8):1173-5. View Abstract
Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes. J Pediatr Surg. 2004 Jun; 39(6):834-8; discussion 834-8. View Abstract
Rapidly polymerizing hydrogel prevents balloon dislodgement in a model of fetal tracheal occlusion. J Pediatr Surg. 2004 Apr; 39(4):557-60. View Abstract
Hyperoncotic enhancement of pulmonary growth after fetal tracheal occlusion: a comparison between dextran and albumin. J Pediatr Surg. 2004 Mar; 39(3):324-8; discussion 324-8. View Abstract
Local anesthetics inhibit uterine activity in vitro. Possible application on preterm labor prevention and treatment. Fetal Diagn Ther. 2003 Sep-Oct; 18(5):292-6. View Abstract
Fetal tissue engineering: in vitro analysis of muscle constructs. J Pediatr Surg. 2003 Sep; 38(9):1348-53. View Abstract
Serial transverse enteroplasty for short bowel syndrome: a case report. J Pediatr Surg. 2003 Jun; 38(6):881-5. View Abstract
Fetal tracheal augmentation with cartilage engineered from bone marrow-derived mesenchymal progenitor cells. J Pediatr Surg. 2003 Jun; 38(6):984-7. View Abstract
Tissue engineering: current state of clinical application. Curr Opin Pediatr. 2003 Jun; 15(3):267-71. View Abstract
Fetal tissue engineering from amniotic fluid. J Am Coll Surg. 2003 Apr; 196(4):592-7. View Abstract
Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg. 2003 Mar; 38(3):425-9. View Abstract
Clostridium botulinum toxin inhibits myometrial activity in vitro: possible application on the prevention of preterm labor after fetal surgery. J Pediatr Surg. 2003 Mar; 38(3):511-3. View Abstract
Engineered fetal cartilage: structural and functional analysis in vitro. J Pediatr Surg. 2002 Dec; 37(12):1720-5. View Abstract
The placenta as a cell source in fetal tissue engineering. J Pediatr Surg. 2002 Jul; 37(7):995-9; discussion 995-9. View Abstract
Fetal tissue engineering: in utero tracheal augmentation in an ovine model. J Pediatr Surg. 2002 Jul; 37(7):1000-6; discussion 1000-6. View Abstract
The littlest patient. Sciences (New York). 1999 Jul-Aug; 39(4):34-8. View Abstract
Prolonged local myometrial blockade prevents preterm labor after fetal surgery in a leporine model. J Pediatr Surg. 1999 Apr; 34(4):540-2. View Abstract
Fetal response to neutral gas and liquid media for intraamniotic distension. J Pediatr Surg. 1999 Apr; 34(4):591-4. View Abstract
Management of biliary atresia in the liver transplantation era: a 15-year, single-center experience. J Pediatr Surg. 1998 Jan; 33(1):115-8. View Abstract
ECMO in evolution: the impact of changing patient demographics and alternative therapies on ECMO. J Pediatr Surg. 1996 Aug; 31(8):1116-22; discussion 1122-3. View Abstract
Resection of a massive sacrococcygeal teratoma using hypothermic hypoperfusion: a novel use of extracorporeal membrane oxygenation. J Pediatr Surg. 1995 Nov; 30(11):1557-9. View Abstract
Fate of the reconstructed carotid artery after extracorporeal membrane oxygenation. J Pediatr Surg. 1995 Jul; 30(7):1046-9. View Abstract
Congenital diaphragmatic hernia and associated anomalies: their incidence, identification, and impact on prognosis. J Pediatr Surg. 1994 Aug; 29(8):1113-7. View Abstract
Surgically produced congenital diaphragmatic hernia in fetal rabbits. J Pediatr Surg. 1994 Jul; 29(7):882-6. View Abstract
Antenatal diagnosis of isolated congenital diaphragmatic hernia is not an indicator of outcome. J Pediatr Surg. 1994 Jun; 29(6):815-9. View Abstract
Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg. 1994 Feb; 29(2):248-56; discussion 256-7. View Abstract
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[Prevention of tracheo-innominate fistula following tracheostomy: anatomic relations of the trachea and brachiocephalic trunk]. Rev Hosp Clin Fac Med Sao Paulo. 1988 Jan-Feb; 43(1):71-4. View Abstract