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Histochemistry and Cell Biology

, Volume 105, Issue 6, pp 415–429 | Cite as

Placental villous stroma as a model system for myofibroblast differentiation

  • Gaby Kohnen
  • Sonja Kertschanska
  • Ramazan Demir
  • Peter Kaufmann
Original Paper

Abstract

Different subtypes of myofibroblasts have been described according to their cytoskeletal protein patterns. It is quite likely that these different subtypes represent distinct steps of differentiation. We propose the human placental stem villi as a particularly suitable model to study this differentiation process. During the course of pregnancy, different types of placental villi develop by differentiation of the mesenchymal stroma surrounding the fetal blood vessels. In order to characterise the differentiation of placental stromal cells in the human placenta, the expression patterns of the cytoskeletal proteins vimentin, desmin, α- and γ-smooth muscle actin, pan-actin, smooth muscle myosin, and the monoclonal antibody GB 42, a marker of myofibroblasts, were investigated on placental tissue of different gestational age (7th–40th week of gestation). Proliferation patterns were assessed with the proliferation markers MIB 1 and PCNA. Additionally, dipeptidyl peptidase IV distribution was studied in term placenta and the ultrastructure of placental stromal cells was assessed by electron microscopy. Different subpopulations of extravascular stromal cells were distinguished according to typical co-expression patterns of cytoskeletal proteins. Around the fetal stem vessels in term placental villi they were arranged as concentric layers with increasing stage of differentiation. A variable layer of extravascular stromal cells lying beneath the trophoblast expressed vimentin (V) or vimentin and desmin (VD). They were mitotically active. The next layer co-expressed vimentin, desmin, and α-smooth muscle actin (VDA). More centrally towards the fetal vessels, extravascular stromal cells co-expressed vimentin, desmin, α- and γ-smooth muscle actin, and GB 42 (VDAG). Cells close to the fetal vessels additionally co-expressed smooth muscle myosin (VDAGM). Ultrastructurally, V cells resembled typical mesenchymal cells. VD cells corresponded to fibroblasts, while VDA and VDAG cells developed features of myofibroblasts. Cells of the VDAGM-type revealed a smooth muscle cell-related ultrastructure. In earlier stages of pregnancy, stromal cell types with less complex expression patterns prevailed. The media smooth muscle cells of the fetal vessels showed a mixture of different co-expression patterns. These cells were separated from extravascular stromal cells by a layer of collagen fibres. The results obtained indicate a clearly defined spatial differentiation gradient with increasing cytoskeletal complexity in human placental stromal cells from the superficial trophoblast towards the blood vessels in the centre of the stem villi. The spatial distribution of the various stages of differentiation suggests that human placental villi could be a useful model for the study of the differentiation of myofibroblasts.

Keywords

Cytoskeletal Protein Smooth Muscle Myosin Placental Villus Medium Smooth Muscle Cell Fetal Vessel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Atherton AJ, Monaghan P, Warburton MJ, Robertson D, Kenny AJ, Gusterson BA (1992) Dipeptidyl peptidase IV expression identifies a functional sub-population of breast fibroblasts. Int J Cancer 50:15–19PubMedGoogle Scholar
  2. Atherton AJ, Anbazhagan R, Monaghan P, Bartek J, Gusterson BA (1994) Immunolocalisation of cell surface peptidases in the developing breast. Differentiation 56:101–106PubMedGoogle Scholar
  3. Beham A, Denk H, Desoye G (1988) The distribution of intermediate filament proteins, actin and desmoplakins in human placental tissue as revealed by polyclonal and monoclonal antibodies. Placenta 9:479–492PubMedGoogle Scholar
  4. Benirschke K, Kaufmann P (1995) Pathology of the human placenta, 3rd edn. Springer: New York Berlin HeidelbergGoogle Scholar
  5. Benzonana G, Skalli O, Gabbiani G (1988) Correlation between the distribution of smooth muscle or non-muscle myosins and α-smooth muscle actin in normal and pathological soft tissues. Cell Motil Cytoskeleton 11:260–274PubMedGoogle Scholar
  6. Buoro S, Ferrarese P, Chiavegato A, Roclofs M, Scatena M, Pauletto, P, Passerini Glazel G, Pagano F, Sartore S (1993) Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab Invest 69:589–602PubMedGoogle Scholar
  7. Castellucci M, Kaufmann P (1982) Evolution of the stroma in human chorionic villi throughout pregnancy. Bibl Anat 22:40–45PubMedGoogle Scholar
  8. Castellucci M, Sheper M, Scheffen I, Celona A, Kaufmann P (1990) The development of the human placental villous tree. Anat Embryol 181:117–128PubMedGoogle Scholar
  9. Chiavegato A, Bochaton-Piallat ML, D'Amore E, Sartore S, Gabbiani G (1995) Expression of myosin heavy chain isoforms in mammary epithelial cells and in myofibroblasts from different fibrotic settings during neoplasia. Virchows Arch 426:77–86PubMedGoogle Scholar
  10. Darby I, Skalli O, Gabbiani G (1990) α-Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest 63:21–29PubMedGoogle Scholar
  11. Davidoff MS, Breucker H, Holstein AF, Seidl K (1990) Cellular architecture of the lamina propria of human seminiferous tubules. Cell Tissue Res 262:253–261PubMedGoogle Scholar
  12. Demir R, Demir N, Kohnen G, Kosanke G, Mironov V, Üstünel I, Kocamaz E (1992) Ultrastructure and distribution of myofibroblast-like cells in human placental stem villi. Electron Microsc 3:509–510Google Scholar
  13. Demir R, Kosanke G, Kohnen G, Kertschanska S, Kaufmann P Classification of human placental stem villi: structural and functional aspects — a review. Microsc Res Tech (in press)Google Scholar
  14. Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111PubMedGoogle Scholar
  15. Dubreuil G, Rivière M (1932) Formations fibro-musculaires du chorion et des villosités du placenta humain. C R Soc Biol III:170–172Google Scholar
  16. Eddinger TJ, Murphy RA (1991) Developmental changes in actin and myosin heavy chain isoform expression in smooth muscle. Arch Biochem Biophys 284:232–237PubMedGoogle Scholar
  17. Feller AC, Schneider H, Schmidt D, Parwaresch MR (1985) Myofibroblasts as a major cellular constituent of villous stroma in human placenta. Placenta 6:405–415PubMedGoogle Scholar
  18. Frid MG, Printesva OY, Chiavegato A, Faggin E, Scatena M, Koteliansky VE, Pauletto P, Glukhova MA, Sartore S (1993) Myosin heavy-chain isoform composition and discribution in developing and adult human aortic smooth muscle. J Vasc Res 30:279–292PubMedGoogle Scholar
  19. Frid MG, Moiseeva EP, Stenmark KR (1994) Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo. Circ Res 75:669–681PubMedGoogle Scholar
  20. Gabbiani G, Majno G (1972) Dupuytren's contracture: fibroblast contraction? An ultrastructural study. Am J Pathol 66:131–146PubMedGoogle Scholar
  21. Gabbiani G, Ryan GB, Majno G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27:549–550PubMedGoogle Scholar
  22. Giloh H, Sedat JW (1982) Fluorescence microscopy: reduced photobleaching of rhodamine and fluorescein protein conjugates byn-propyl gallate. Science 217:1252–1255PubMedGoogle Scholar
  23. Graf R, Frank HG, Öney T (1992) Histochemical and immunocytochemical investigations of the fetal extravascular and vascular contractile system in the normal placenta and during preeclampsia. In: Neubert D, Kavlock RJ, Merker HJ, Klein J (eds) Risk assessment of prenatally-induced adverse health effects. Springer, Heidelberg Berlin New York, pp 537–550Google Scholar
  24. Graf R, Langer JU, Schönfelder G, Öney T, Hartel-Schenk S, Reutter W, Schmidt HHHW (1994) The extravascular contractile system in the human placenta. Morphological and immunocytochemical investigations. Anat Embryol 190:541–548PubMedGoogle Scholar
  25. Graham CH, Lysiak JJ, McCrae KR Lala PK (1992) Localization of transforming growth factor-β at the human fetal-maternal interface: role in trophoblast growth and differentiation. Biol Reprod 46:561–572PubMedGoogle Scholar
  26. Güldner FH, Wolff JR, Graf Keyserlingk D (1972) Fibroblasts as a part of the contractile system in duodenal villi of rat. Z Zellforsch 135:349–360PubMedGoogle Scholar
  27. Hartel S, Gossrau R, Hanski C, Reutter W (1988) Dipetidyl peptidase (DPP) IV in rat organs. Comparison of immunohisto-chemistry and activity histochemistry. Histochemistry 89:151–161PubMedGoogle Scholar
  28. Hartel-Schenk S, Gossrau R, Reutter W (1990) Comparative immunohistochemistry and histochemistry of dipeptidyl peptidase IV in rat organs during development. Histochem J 22: 567–578PubMedGoogle Scholar
  29. Hayward LJ, Schwartz RJ (1980) Sequential expression of chicken actin genes during myogenesis. J Cell Biol 102:1485–1493Google Scholar
  30. Hsi BL, Yeh CJG (1987) Studies of Clq deposits in the human placenta using monoclonal antibodies to human extra-embryonic tissues. Trophoblast Res 2:223–231Google Scholar
  31. Hsi BL, Yeh CJG (1988) Monoclonal antibodies to placental vascular structures. Trophoblast Res 3:139–148Google Scholar
  32. Hunt JS (1989) Macrophages in human uteroplacental tissues: a review. Am J Reprod Immunol 21:119–122PubMedGoogle Scholar
  33. Kapanci Y, Burgan S, Pietra GG Conne B, Gabbiani G (1990) Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol 136:881–889PubMedGoogle Scholar
  34. Kaufmann P, Stark J, Stegner HE (1977) The villous stroma of the human placenta. I. The ultrastructure of fixed connective tissue cells. Cell Tissue Res 177:105–121PubMedGoogle Scholar
  35. Kaufmann P, Sen DK, Schweikhart C (1979) Classification of human placental villi. I. Histology. Cell Tissue Res 200:409–423PubMedGoogle Scholar
  36. Khong TY, Lane EB, Robertson WB (1986) An immunocytochemical study of fetal cells at the maternal-placental interface using monoclonal antibodies to keratins, vimentin and desmin. Cell Tissue Res 246:189–195PubMedGoogle Scholar
  37. Kocher O, Skalli O, Cerutti D, Gabbiani F, Gabbiani G (1985) Cytoskeletal features of rat aortic cells during development. Circ Res 56:829–838PubMedGoogle Scholar
  38. Kohnen G, Mironov V, Demir R, Hsi BL, Castellucci M, Kaufmann P (1992) Development and classification of human placental stem villi (abstract). Placenta 13:A35Google Scholar
  39. Kohnen G, Castellucci M, Graf R, Kaufmann P (1993) Contractile filaments of extravascular stromal cells in human placental stem villi (abstract). Placenta 14:A38Google Scholar
  40. Kohnen G, Castellucci M, Hsi BL, Yeh CJG, Kaufmann P (1995) The monoclonal antibody GB 42 — a useful marker for the differentiation of myofibroblasts. Cell Tissue Res 281:231–242PubMedGoogle Scholar
  41. Krantz KE, Parker JC (1963) Contractile properties of the smooth muscle in the human placenta. Clin Obstet Gynecol 6:26–38Google Scholar
  42. Kuhn C, McDonald JA (1991) The roles of the myofibroblast in idiopathic pulmonary fibrosis. Am J Pathol 138:1257–1265PubMedGoogle Scholar
  43. Kuro-o M, Nagai R, Tsuchimochi H, Katoh H, Yazaki Y, Ohkubo A, Takaku F (1989) Developmentally regulated expression of vascular smooth muscle myosin heavy chain isoforms. J Biol Chem 264:18272–18275PubMedGoogle Scholar
  44. Lazard D, Sastre X, Frid MG, Glukhova MA, Thiery JP, Koteliansky VE (1993) Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue. Proc Natl Acad Sci USA 90:999–1003PubMedGoogle Scholar
  45. Leslie KO, Mitchell J, Low R (1992) Views and reviews. Lung myofibroblasts. Cell Motil Cytoskeleton 22:92–98PubMedGoogle Scholar
  46. Lipper S, Kahn LB, Reddick RL (1980) The myofibroblast. Pathol Annu 15:409–441PubMedGoogle Scholar
  47. Lojda Z, Gossrau R, Stoward PJ (1991) Proteases. In: Stoward PJ, Pearse AGE (eds) Histochemistry. Theoretical and applied, vol. 3. Enzyme histochemistry, 4th edn. Churchill Livingstone. Edinburgh, pp 305–309Google Scholar
  48. Majno G, Gabbiani G, Hirschel BJ Ryan GB, Statkov PR (1971) Contraction of granulation tissue in vitro: similarity to smooth muscle. Science 173:548–550PubMedGoogle Scholar
  49. McHugh KM, Lessard JL (1988) The development expression of the rat α-vascular and γ-enteric smooth muscle isoactins isolation and characterization of a rat γ-enteric actin cDNA. Mol Cell Biol 8:5224–5231PubMedGoogle Scholar
  50. McHugh KM, Crawford K, Lessard JL (1991) A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. Dev Biol 148:442–458PubMedGoogle Scholar
  51. Muijen GNP van, Ruiter DJ, Warnaar SO (1987) Coexpression of intermediate filament polypeptides in human fetal and adult tissues. Lab Invest 57:359–369PubMedGoogle Scholar
  52. Osborn M, Weber K (1983) Biology of disease. Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. Lab Invest 48:372–394PubMedGoogle Scholar
  53. Ross R, Klebanoff SJ (1967) Fine structural changes in uterine smooth muscle and fibroblasts in response to estrogen. J Cell Biol 32:155–167PubMedGoogle Scholar
  54. Ryan GB, Cliff WJ, Gabbiani G, Irle C, Statkov PR, Majno G (1973) Myofibroblasts in an avascular fibrous tissue. Lab Invest 29:197–206PubMedGoogle Scholar
  55. Saison M, Verlinden J, Leuven F van, Cassiman JJ, Berghe H van den (1983) Identification of cell surface dipeptidylpeptidase IV in human fibroblasts. Biochem J 216:177–183PubMedGoogle Scholar
  56. Sappino AP, Skalli O, Jackson B, Schürch W, Gabbiani G (1988) Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer 41:707–712PubMedGoogle Scholar
  57. Sappino AP, Schürch W, Gabbiani G (1990) Biology of disease. Differentiation repertoire of tibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63:144–161PubMedGoogle Scholar
  58. Schürch W, Seemayer TA, Lagacé R (1981) Stromal myofibroblasts in primary invasive and metastatic carcinomas. Virchows Arch [A] 391:125–139Google Scholar
  59. Scott RF, Jones R, Daond AS (1967) Experimental atherosclerosis in rhesus monkeys: II. Cellular clements of proliferative lesions and possible role of cytoplasmic degeneration in pathogenesis as studied by electron microscopy. Exp Mol Pathol 7:34–57PubMedGoogle Scholar
  60. Seemayer TA, Lagacé R, Schürch W, Thelmo WL (1980) The myofibroblast: biologic, pathologic and theoretical considerations. Pathol Annu 15:443–470PubMedGoogle Scholar
  61. Skalli O, Gabbiani G (1988) The biology of the myofibroblast. Relationship to wound contraction and fibrocontractive diseases. In: Clark RAF, Henson PM (eds) The molecular and cellular biology of wound repair. Plenum, New York, pp 373–402Google Scholar
  62. Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol 103:2787–2796PubMedGoogle Scholar
  63. Skalli O, Vandekerckhove J, Gabbiani G (1987) Actin-isoform pattern as a marker of normal or pathological smooth-muscle and fibroblastic tissues. Differentiation 33:232–238PubMedGoogle Scholar
  64. Skalli O, Schürch W, Seemayer T, Lagacé R, Mantandon D, Pittet B, Gabbiani G (1989) Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest 60:275–285PubMedGoogle Scholar
  65. Spanner R (1936) Mütterlicher und kindlicher Kreislauf der menschlichen Placenta und seine Strombahnen. Z Anat Entwicklungsgesch 105:163–242Google Scholar
  66. Sparn HG, Lieder-Ochs BA, Franke WW (1994) Immunohistochemical identification and characterization of a special type of desmin-producing stromal cells in human placenta and other fetal tissues. Differentiation 56:191–199PubMedGoogle Scholar
  67. Sporn MB, Roberts AB, Wakefield LM, Crombrugghe B de (1987) Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105:1039–1045PubMedGoogle Scholar
  68. Stein H, Schwarting R, Niedobitek G (1989) Cluster report: CD26. In: Knapp W, Dörken B, Gilks WR, Rieber EP, Schmitt RE, Stein H, Borne AEGK von dem (eds) Leucocyte typing IV. White cell differentiation antigens. Oxford University Press. New York, pp 412–415Google Scholar
  69. Ulmer AJ, Mattern T, Feller AC, Heymann E, Flad HD (1990) CD 26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7. Scand J Immunol 31:429–435PubMedGoogle Scholar
  70. Vandekerckhove J, Weber K (1978) At least six different actins are expressed in a higher mammal: an analysis based on the amino acid sequence of the amino-terminal tryptic peptide. J Mol Biol 126:783–802PubMedGoogle Scholar
  71. Vandekerckhove J, Weber K (1979) The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. Differentiation 14:123–133PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Gaby Kohnen
    • 1
  • Sonja Kertschanska
    • 1
  • Ramazan Demir
    • 2
  • Peter Kaufmann
    • 1
  1. 1.Department of AnatomyRWTH AachenAachenGermany
  2. 2.Department of Histology and EmbryologyAkdeniz UniversityAntalyaTurkey

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