Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000072.xml
Semin Reprod Med 2006; 24(5): 348-357
DOI: 10.1055/s-2006-952156
DOI: 10.1055/s-2006-952156
In Utero Stem Cell Transplantation
Magnus Westgren1Further Information
Publication History
Publication Date:
22 November 2006 (online)
ABSTRACT
Successful in utero stem cell transplantations with hematopoietic or other stem cells should represent a major step forward in the management of patients with congenital, hematological, metabolic, and immunological disorders. The possibility of performing cell transplantations with stem cells across histoincompatibility barriers without chemotherapy has great potential for both pre and postnatal transplantations. The present article includes an overview of this topic with special reference to different animal models and the experience in humans in regard to fetal stem cell transplantations.
This area of research holds great promise for the future, and development of efficient intrauterine stem cell treatment may enable the relative new speciality of fetal medicine to progress from a mainly diagnostic to a therapeutic medical subject.
KEYWORDS
Stem cell - fetal transplantation - fetal therapy - hematopoietic stem cell - mesenchymal stem cell
REFERENCES
- 1 Davies J. A case of haemolytic disease with congenital rubella. BMJ. 1967; 2 819-822
- 2 Touraine J L, Royo C, Roncarolo M G, Murray K, de Boutciller O. Unmatched stem cell transplantations as a possible alternative to bone marrow transplantation. Transplant Proc. 1989; 21 3197-3198
- 3 Flake A W, Roncarolo J M, Puck G et al.. Treatment of X-linked severe combined immunodeficiency by in utero transplantation of paternal bone marrow. N Engl J Med. 1996; 335 1806-1810
- 4 Lanfranchini A, Neva A, Tettoni K, Veradi R, Mazzollari E, Wengler G. In utero transplantation (IUT) of parental CD34 + cells in patient affected by primary immunodeficiencies. Bone Marrow Transplant. 1998; 21 S127-128
- 5 Westgren M, Ringdén O, Bartmann P et al.. Prenatal T-cell reconstitution after in utero transplantation with fetal liver cells in a patient with X-linked severe combined immunodeficiency. Am J Obstet Gynecol. 2002; 187 475-482
- 6 Shields L E, Lindton B, Andrews R G, Westgren M. Fetal hematopoietic stem cell transplantation: a challenge for the twenty-first century. J Hematother Stem Cell Res. 2002; 11 617-631
- 7 Flake A W. Genetic therapies for the fetus. Clin Obstet Gynecol. 2002; 45 684-696
- 8 Flake A W. In utero stem cell transplantation. Clin Obstet Gynecol. 2002; 45 941-958
- 9 Jolly R D, Thompson K G, Murphy C E, Manktelow B W, Bruere A N, Winchester B G. Enzyme replacement therapy-an experiment of nature in chimeric mannosidosis calf. Pediatr Res. 1976; 10 219-224
- 10 Owen R D. Immunogenetic consequences of vascular anastomoses between bovine twins. Science. 1945; 102 400-401
- 11 Jones M Z, Cavanagh K T, Kranich R et al.. Possible beta-mannosidosis chimera. Altered expression of metabolic perturbations. J Inherit Metab Dis. 1993; 16 1012-1023
- 12 Picus J, Aldrich W R, Levin N L. A naturally occurring bone-marrow-chimeric primate. I. Integrity of its immune system. Transplantation. 1985; 39 297-303
- 13 Howell J M, Dorling P R, Shelton J N, Taylor E G, Palmer D G, Di Marco P N. Natural bone marrow transplantation in cattle with PompeŽs disease. Neuromuscul Disord. 1991; 1 449-454
- 14 Emery D, McCullagh P. Immunological reactivity between chimeric cattle twins. I. Homograft reaction. Transplantation. 1980; 29 4-9
- 15 van Dijk B A, Boomsma D I, de Man A J. Blood group chimerism in human multiple births is not rare. Am J Med Genet. 1996; 61 264-268
- 16 Hansen H E, Niebuhr E, Lomas C. Chimeric twins. T.S. and M.R. reexamined. Hum Hered. 1984; 34 127-130
- 17 Fleischman R A, Mintz B. Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta. Proc Natl Acad Sci USA. 1979; 76 5736-5740
- 18 Blazar B R, Taylor P A, Vallera D A. In utero transfer of adult bone marrow cells into recipients with severe combined immunodeficiency disorder yields lymphoid progeny with T- and B-cell functional capabilities. Blood. 1995; 86 4353-4366
- 19 Archer D R, Turner C W, Yeager A M, Fleming W H. Sustained multilineage engraftment of allogeneic hematopoietic stem cells in NOD/SCID mice after in utero transplantation. Blood. 1997; 90 3222-3229
- 20 Carrier E, Lee T H, Busch M P, Cowan M J. Induction of tolerance in nondefective mice after in utero transplantation of major histocompatibility complex-mismatched fetal hematopoietic stem cells. Blood. 1995; 86 4681-4690
- 21 Hajdu K, Tanigawara S, McLean L K, Cowan M J, Golbus M S. In utero allogeneic hematopoietic stem cell transplantation to induce tolerance. Fetal Diagn Ther. 1996; 11 241-248
- 22 Howson J K, Matloub Y H, Vallera D A, Blazar B R. In utero engraftment of fully H-2-incompatible versus congenic adult bone marrow transferred into nonanemic or anemic murine fetal recipients. Transplantation. 1993; 56 709-716
- 23 Flake A, Harrison M R, Adzick N S, Zanjani N D. Transplantation of fetal hematopoietic stem cells in utero: the creation of hematopoietic chimeras. Science. 1986; 223 776-778
- 24 Zanjani E D, Ruthven A, Ruthven J, Shaft D, Smith D, Flake A W. In utero hematopoietic stem cell transplantation results in donor specific tolerance and facilitates postnatal “boosting” of donor cell levels. Blood. 1994; 84 100a
- 25 Zanjani E D, Almeida-Porada G, Ascensao J L, MacKintosh F R, Flake A W. Transplantation of hematopoietic stem cells in utero. Stem Cells. 1997; 15 79-93
- 26 Crombleholme T M, Harrison M R, Zanjani E D. In utero transplantation of hematopoietic stem cells in sheep: the role of T cells in engraftment and graft-versus-host disease. J Pediatr Surg. 1990; 25 885--892
- 27 Westlake V, Jolly R, Jones B et al.. Hematopoietic cell transplantation in fetal lambs with ceroid-lipofuscinosis. Am J Med Genet. 1995; 57 365-368
- 28 Pearce R D, Kiehm D, Armstrong D T et al.. Induction of hematopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells. Experientia. 1989; 45 307-308
- 29 Blakemore K, Hattenburg C, Stetten G et al.. In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model. Am J Obstet Gynecol. 2004; 190 960-970
- 30 Harrison M. In utero transplantation of fetal liver hematopoietic stem cells in monkeys. Lancet. 1989; 2 1425-1427
- 31 Roodman G D, Kuehl T J, Vandeberg O L, Muirhead D Y. In utero bone marrow transplantation of fetal baboons with mismatched adult baboon marrow. Blood Cells. 1991; 17 367-375
- 32 Brent L, Linch D C, Rodeck C H et al.. On the feasibility of inducing tolerance in man: a study in the cynomolgus monkey. Immunol Lett. 1989; 21 55-61
- 33 Cowan M J, Tarantal A F, Capper J, Harrison M, Garovoy M. Long-term engraftment following in utero T cell-depleted parental marrow transplantation into fetal rhesus monkeys. Bone Marrow Transplant. 1996; 17 1157-1165
- 34 Shields L E, Gaur L K, Gough M, Potter J, Sieverkropp A, Andrews R G. In utero hematopoietic stem cell transplantation in nonhuman primates: the role of T cells. Stem Cells. 2003; 21 304-314
- 35 Shields L E, Andrews R G. In utero stem cell transplantation in non-human primates: the role of T-cell number. Am J Obstet Gynecol. 2001; 184 S2
- 36 Shields L E, Gauer L, Delio P, Potter J, Sieverkropp A, Andrews R G. Fetal immune suppression as adjunctive therapy for in utero hematopoietic stem cell transplantation in nonhuman primates. Stem Cells. 2004; 22 759-769
- 37 Kim H B, Shaaban A F, Milner R et al.. In utero bone marrow transplantation induces tolerance by a combination of clonal deletion and anergy. J Pediatr Surg. 1999; 34 726-730
- 38 Kim H B, Shaaban A F, Yang E Y et al.. Microchimerism and tolerance after in utero bone marrow transplantation in mice. J Surg Res. 1998; 77 1-5
- 39 Harrison D E, Zhong R K, Jordan C T et al.. Relative to adult marrow, fetal liver repopulates nearly five times more effectively long-term than short-term. Exp Hematol. 1997; 25 293-297
- 40 Shields L E, Andrews R G, Westgren M, Broliden K. In vitro hematopoiesis is inhibited in humans and non-human primates by recombinant parvo virus capsid. Am J Obstet Gynecol. 2000; 182 S18
- 41 Norbeck O, Tolvenstam T, Shields L E, Westgren M, Broliden K. Parvovirus B19 capsid protein VP2 inhibits hematopoiesis in vitro and in vivo: implications for therapeutic use. Exp Hematol. 2004; 32 1082-1087
- 42 Almeida-Porada G, Flake A W, Glimp H A, Zanjani E D. Cotransplantation of stroma results in enhancement of engraftment and early expression of donor hematopoietic stem cells in utero. Exp Hematol. 1999; 27 1569-1575
- 43 Almeida-Porada G, Porada C D, Tran N, Zanjani E D. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000; 95 3620-3627
- 44 Flake A, Zanjani E. In utero hematopoietic stem cell transplantation: ontogenic opportunities and biological barriers. Blood. 1999; 94 2179-2191
- 45 Renda M C, Fecarotta E, Dieli F et al.. Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation. Bone Marrow Transplant. 2000; 25 135-141
- 46 Toivanen P, Uksila J, Leino A, Lassila O, Hirvonen T, Ruuskanen O. Development of mitogen responding T cells and natural killer cells in the human fetus. Immunol Rev. 1981; 57 89-105
- 47 Sites D P, Carr M C, Fudenberg H H. Ontogeny of cellular immunity in the human fetus: development of responses to phytohemaglutinin and to allogeneic cells. Cell Immunol. 1974; 11 257-271
- 48 Lindton B, Markling L, Ringden O, Westgren M. In vitro studies of the role of CD3 + and CD56 + cells in fetal liver cell alloreactivity. Transplantation. 2003; 76(1) 204-209
- 49 Götherström C, Johnsson A M, Mattsson J, Papadogiannakis N, Westgren M. Identification of maternal hematopoietic cells in a 2nd trimester fetus. Fetal Diagn Ther. 2005; 20 355-358
- 50 Burk R. Clinical utility in maximizing CD 34 + cell count in stem cell grafts. Stem Cells. 1999; 17 373-376
- 51 Shields L E, Andrews R G. Gestational age changes in circulating CD34 + hematopoietic stem/progenitor cells in fetal cord blood. Am J Obstet Gynecol. 1998; 178 931-937
- 52 Shields L E, Gaur L, Delio P et al.. The use of CD 34(+) mobilized peripheral blood as a donor cell source does not improve chimerism after in utero hematopoietic stem cell transplantation in non-human primates. J Med Primatol. 2005; 34 (4) 201-208
- 53 Hayward A, Ambruso D, Battaglia F et al.. Microchimerism and tolerance following intrauterine transplantation and transfusion for alpha-thalassemia-1. Fetal Diagn Ther. 1998; 13 8-14
- 54 Westgren M, Ringdén O, Eik Nes S et al.. Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies. Transplantation. 1996; 61 1176-1179
- 55 Diukman R, Golbus M. In utero stem cell therapy. J Reprod Med. 1992; 37 515-520
- 56 Slavin S, Naparstek E, Ziegler M, Lewin A. Clinical application of intrauterine bone marrow transplantation for treatment of genetic diseases-feasibility studies. Bone Marrow Transplant. 1992; 9 189-190
- 57 Touraine J L, Raudrant D, Royo C et al.. In utero transplantation of hematopoietic stem cells in humans. Transplant Proc. 1991; 23 1706-1708
- 58 Peschle C. In utero transplantation of purified stem cells from an HLA-identical sibling into a beta-thalassemia embryo. Paper presented at: Second International Meeting for In Utero Stem Cell Transplantation and Gene Therapy January 15, 1997 Nottingham, United Kingdom;
- 59 Linch D, Rodeck C, Nicolaides K, Jones H, Brent L. Attempted bone-marrow transplantation in a 17-week fetus. Lancet. 1986; 2 1453
- 60 Thilaganathan B, Nicolaides K H, Morgan G. Subpopulations of CD34-positive hematopoietic progenitors in fetal blood. Br J Haematol. 1994; 87 634-636
- 61 Wengler G S, Lanfranchi T, Frusca R et al.. In-utero transplantation of parental CD34 hematopoietic progenitor cells in a patient with X-linked severe combined immunodeficiency (SCIDXI). Lancet. 1996; 348 1484-1487
- 62 Muench M O, Rae I, Barcena A et al.. Transplantation of a fetus with paternal Thy-1( + )CD34( + )cells for chronic granulomatous disease. Bone Marrow Transplant. 2001; 27 355-364
- 63 Porta F, Mazzolari E, Zucca S et al.. Prenatal transplant in a fetus affected by Omenn syndrome. Bone Marrow Transplant. 2000; 25(suppl) S43-44
- 64 Barnbusch B J, Moser H W, Blakemore K et al.. Engraftment following in utero bone marrow transplantation for globoid cell leucodystrophy. BMT. 1997; 19 399-402
- 65 Leung W, Blakemore K, Jones R J et al.. A human-murine chimera model for in utero human hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 1999; 5 1-7A
- 66 Flake A W, Zanjani E D. In utero hematopoietic stem cell transplantation. A status report. JAMA. 1997; 278 932-937
- 67 Friedenstein A J, Petrakova K V, Kuroksova A I et al.. Heterotopic transplants of bone marrow: analysis of precursor cells for osteogenic and hematopoietic tissue. Transplantation. 1968; 6 230-247
- 68 Prockop D J. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997; 276 71-74
- 69 Haynesworth S E, Goshima J, Goldberg V M et al.. Characterization of cells with osteogenic potential from human marrow. Bone. 1992; 13 81-88
- 70 Devine S M, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into non-human primates. Blood. 2003; 101 2999-3001
- 71 Pittenger M F, Mackay A M, Beck S C et al.. Multi-lineage potential of adult human mesenchymal stem cells. Science. 1999; 284 143-147
- 72 In't Anker P S, Scherjon S A, Kleijburg-van der Keur C et al.. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 2003; 102 1548-1549
- 73 Erices A, Conget P, Minguell J J. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000; 109 235-242
- 74 Lee O K, Kuo T K, Chen W M, Lee K D, Hsieh S L, Chen T H. Isolation of multi-potent mesenchymal stem cells from umbilical cord blood. Blood. 2004; 103 1669-1675
- 75 Pereira R F, Halford K W, O'Hara M D et al.. Cultured adherent cells from marrow can serve as long-lasting precursors for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci USA. 1995; 92 4857-4861
- 76 Liechty K W, MacKenzie T C, Shaaban A F et al.. Human mesenchymal stem cells engraft and demonstrate site specific differentiation after in utero transplantation in sheep. Nat Med. 2000; 6 1282-1286
- 77 Migliaccio G, Migliaccio A R, Petti S et al.. Human embryonic hemopoiesis: kinetics of progenitors and precursors underlying the yolk sack-liver transition. J Clin Invest. 1986; 78 51-60
- 78 Zanjani E D, Ascensao J L, Tavasolli M. Liver-derived fetal hematopoietic stem cells selectively and preferentially home to fetal bone marrow. Blood. 1993; 81 399-404
- 79 Liechty K W, MacKenzie T C, Shaaban A F et al.. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med. 2000; 6 1282-1286
- 80 Mackenzie T C, Flake A W. Human mesenchymal stem cells persist, demonstrate site-specific multipotential differentiation, and are present in sites of wound healing and tissue regeneration after transplantation into fetal sheep. Blood Cells Mol Dis. 2001; 27 601-604
- 81 Schoeberlein A, Holzgreve W, Dudler L, Hahn S, Surbek D V. Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses. Am J Obstet Gynecol. 2005; 192 1044-1052
- 82 Horwitz E M, Prockop D J, Fitzpatrick L A et al.. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 1999; 5 309-313
- 83 Horwitz E M, Gordon P L, Koo W K et al.. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesism imperfecta. Proc Natl Acad Sci USA. 2002; 99 8932-8937
- 84 Le Blanc K, Götherström C, Ringdén O et al.. Fetal mesenchymal stem cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation. 2005; 79 1607-1614
- 85 Di Nicola M, Carlo-Stella C, Magni M et al.. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or non-specific mitogenic stimuli. Blood. 2002; 99 3838-3843
- 86 Götherström C, Ringden O, Tammik C, Zetterberg E, Westgren M, Le Blanc K. Immunological properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol. 2004; 190 239-245
- 87 Götherström C, Ringdén O, Westgren M, Tammik L, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant. 2003; 32 265-272
- 88 Götherström C, West A, Liden J, Uzunel M, Lahesmaa R, Le Blanc K. Difference in gene expression between human fetal liver and adult bone marrow mesenchymal stem cells. Haematologica. 2005; 90 1017-1026
- 89 Cubert R, Cheng E Y, Mack S et al.. Osteogenesis imperfecta: mode of delivery and neonatal outcome. Obstet Gynecol. 2001; 97 66-69
- 90 Kaur C, Hao A J, Wu C H, Ling E A. Origin of microglia. Microsc Res Tech. 2001; 54 2-9
- 91 Gussoni E, Blau H M, Kunkel L M. The fate of individual myoblasts after in utero transplantation into muscles of DMD patients. Nat Med. 1997; 3 970-977
- 92 De Bari C, Delláccio F, Vandenabeele F et al.. Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. J Cell Biol. 2003; 160 909-918
- 93 In't Anker P, Noort W, Scherjon S et al.. Mesenchymal stem cells in human second trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogenous multilineage differentiation potential. Haematologica. 2003; 88 845-852
- 94 In't Anker P, Noort W A, Kruisserbrink A B et al.. Nonexpanded primary lung and bone marrow derived mesenchymal cells promote the engraftment of umbilical cord blood derived CD 34 + cells in NOD/SCID mice. Exp Hematol. 2003; 31 881-889
- 95 Campagnoli C, Roberts I A, Kumar S et al.. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001; 98 2396-2402
- 96 Sasaki K, Nagao Y, Kitano Y et al.. Hematopoietic microchimerism in sheep after in utero transplantation of cultured cynomolgus embryonic stem cells. Transplantation. 2005; 79 (1) 32-37
- 97 Nava S, Westgren M, Jakesh M et al.. Characterization of cells in the developing human liver. Differentiation. 2005; 73 249-260
- 98 Nowak G, Ericzon B G, Nava S, Jakesch M, Westgren M, Sumitral-Holgersson S. Identification of expandable human progenitors which differentiate into mature hepatic cells in vivo. Gut. 2005; 54 972-979
- 99 Orlandi F, Giambona A, Messana F et al.. Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy after in utero fetal transplantation. Bone Marrow Transplant. 1996; 18 637-639
- 100 Thilaganthan B, Nicoliades K. Intrauterine bone-marrow transplantation a gestation. Lancet. 1993; 342 243
- 101 Touraine J L, Raudrant D, Laplace S. Transplantation of hematopoietic cells from the fetal liver to treat patients with congenital diseases postnatally or prenatally. Transplant Proc. 1997; 29 712-713
- 102 Bambach B J, Moser H W, Blakemore K et al.. Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy. Bone Marrow Transplant. 1997; 19 399-402
- 103 Monni G, Ibba R M, Zoppi M A, Floris M. In utero stem cell transplantation. Croat Med J. 1998; 39 220-223
Professor
Magnus Westgren
Karolinska Institutet
14186 Stockholm, Sweden
Email: magnus.westgren@klinvet.ki.se