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Tracing CD34+ Stromal Fibroblasts in Palatal Mucosa and Periodontal Granulation Tissue as a Possible Cell Reservoir for Periodontal Regeneration

Published online by Cambridge University Press:  04 June 2015

Alexandra Roman ,
Emőke Páll ,
Carmen M. Mihu ,
Adrian S. Petruţiu ,
Lucian Barbu-Tudoran ,
Radu S. Câmpian ,
Adrian Florea  and
Carmen Georgiu
Alexandra Roman
Affiliation:
Department of Periodontology, Faculty of Dental Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 15 V. Babeş Street, 400012 Cluj-Napoca, Romania
Emőke Páll
Affiliation:
Department of Periodontology, Faculty of Dental Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 15 V. Babeş Street, 400012 Cluj-Napoca, Romania Department of Veterinary Reproduction, Obstetrics and Gynecology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 3-5 Mănăştur Street, 400372 Cluj-Napoca, Romania
Carmen M. Mihu
Affiliation:
Department of Histology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 6 L. Pasteur Street, 400349 Cluj-Napoca, Romania
Adrian S. Petruţiu
Affiliation:
Department of Periodontology, Faculty of Dental Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 15 V. Babeş Street, 400012 Cluj-Napoca, Romania
Lucian Barbu-Tudoran
Affiliation:
Department of Molecular Biology and Biotechnologies, Faculty of Biology and Geology, Babeş-Bolyai University, 5-7 Clinicilor Street, 400006 Cluj-Napoca, Romania
Radu S. Câmpian
Affiliation:
Department of Oral Rehabilitation, Faculty of Dental Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 15 V. Babeş Street, 400012 Cluj-Napoca, Romania
Adrian Florea*
Affiliation:
Department of Cell and Molecular Biology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 6 L. Pasteur Street, 400349 Cluj-Napoca, Romania
Carmen Georgiu
Affiliation:
Department of Pathology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 8 V. Babeş Street, 400012 Cluj-Napoca, Romania
*
*Corresponding author.aflorea@umfcluj.ro; adrian_a_florea@yahoo.com
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Abstract

The aim of the present research was to trace CD34+ stromal fibroblastic cells (CD34+ SFCs) in the palatal connective tissue harvested for muco-gingival surgical procedures and in granulation tissues from periodontal pockets using immunohistochemical and transmission electron microscopy. Immunohistochemical analysis targeted the presence of three antigens: CD31, α-smooth muscle actin (α-SMA), and CD34. In the palate, CD31 staining revealed a colored inner ring of the vessels representing the endothelium, α-SMA+ was located in the medial layer of the vasculature, and CD34 was intensely expressed by endothelial cells and artery adventitial cells (considered to be CD34+ SFCs). Granulation tissue showed the same pattern for CD31+ and α-SMA, but a different staining pattern for CD34. Ultrastructural examination of the palatal tissue highlighted perivascular cells with fibroblast-like characteristics and pericytes in close spatial relationship to endothelial cells. The ultrastructural evaluation of granulation tissue sections confirmed the presence of neovasculature and the inflammatory nature of this tissue. The present study traced the presence of CD34+ SFCs and of pericytes in the palatal connective tissue thus highlighting once more its intrinsic regenerative capabilities. The clinical and systemic factors triggering mobilization and influencing the fate of local CD34+SCFs and other progenitors are issues to be further investigated.

Keywords

tissue graftimmunohistochemistryultrastructureCD34 antigenpericytes
Type
Biological Applications and Techniques
Information
Microscopy and Microanalysis , Volume 21 , Issue 4 , August 2015 , pp. 837 - 848
Copyright
© Microscopy Society of America 2015 

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Footnotes

a

Roman A. and Páll E. equally contributed to the present study and can be regarded, therefore, as being main authors.

References

Allt, G. & Lawrenson, J.G. (2001). Pericytes: Cell biology and pathology. Cells Tissues Organs 169, 1–11.CrossRefGoogle Scholar
Alongi, D.J., Yamaza, T., Song, Y., Fouad, A.F., Romberg, E.E., Shi, S., Tuan, R.S. & Huang, G.T. (2010). Stem/progenitor cells from inflamed human dental pulp retain tissue regeneration potential. Regen Med 5, 617–631.Google Scholar
Andreeva, E.R., Pugach, I.M., Gordon, D. & Orekhov, A.N. (1998). Continuous subendothelial network formed by pericyte-like cells in human vascular bed. Tissue Cell 30, 127–135.Google Scholar
Barth, P.J., Ramaswamy, A. & Moll, R. (2002). CD34(+) fibrocytes in normal cervical stroma, cervical intraepithelial neoplasia III, and invasive squamous cell carcinoma of the cervix uteri. Virchows Arch 441, 564–568.Google Scholar
Barth, P.J. & Westhoff, C.C. (2007). CD34+ fibrocytes: Morphology, histogenesis and function. Curr Stem Cell Res Ther 2, 221–227.Google Scholar
Borghetti, A. & Monett-Corti, V. (2000). La greffe de conjonctif: Indications et prelevement. In Chirurgie plastique parodontale, 1ere ed, CdP, Borghetti, A. & Monett-Corti, V. (Eds.), pp. 209–222. Paris: Editions CdP.Google Scholar
Braun, J., Kurtz, A., Barutcu, N., Bodo, J., Thiel, A. & Dong, J. (2013). Concerted regulation of CD34 and CD105 accompanies mesenchymal stromal cell derivation from human adventitial stromal cell. Stem Cells Dev 22, 815–827.CrossRefGoogle ScholarPubMed
Cairo, F., Pagliaro, U. & Nieri, M. (2008). Treatment of gingival recession with coronally advanced flap procedures: A systematic review. J Clin Periodontol 35, 136–162.Google Scholar
Camelo, M., Nevins, M.L., Schenk, R.K., Simion, M., Rasperini, G., Lynch, S.E. & Nevins, M. (1998). Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodontics Restorative Dent 18, 321–331.Google ScholarPubMed
Chambrone, L., Chambrone, D., Pustiglioni, F.E., Chambrone, L.A. & Lima, L.A. (2008). Can subepithelial connective tissue grafts be considered the gold standard procedure in the treatment of Miller class I and II recession-type defects? J Dent 36, 659–671.Google Scholar
Chen, F.M., Sun, H.H., Lu, H. & Yu, Q. (2012). Stem cell-delivery therapeutics for periodontal tissue regeneration. Biomaterials 33, 6320–6344.Google Scholar
Civin, C.I., Strauss, L.C., Brovall, C., Fackler, M.J., Schwartz, J.F. & Shaper, J.H. (1984). Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol 133, 157–165.CrossRefGoogle Scholar
Corselli, M., Chen, C.W., Sun, B., Yap, S., Rubin, J.P. & Peault, B. (2012). The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells. Stem Cells Dev 21, 1299–1308.Google Scholar
Cortellini, P., Tonetti, M.S., Lang, N.P., Suvan, J.E., Zucchelli, G., Vangsted, T., Silvestri, M., Rossi, R., Mcclain, P., Fonzar, A., Dubravec, D. & Adriaens, P. (2001). The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: Clinical outcomes and postoperative morbidity. J Periodontol 72, 1702–1712.Google Scholar
Díaz-Flores, L., Gutiérrez, R., García, M.P., Sáez, F.J., Díaz-Flores, L.J.R., Valladares, F. & Madrid, J.F. (2014 a). CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology. Histol Histopathol 29, 831–870.Google Scholar
Díaz-Flores, L., Gutiérrez, R., Lizartza, K., Goméz, M.G., García, M.D., Sáez, F.J., Díaz-Flores, L.J.R. & Madrid, J.F. (2014 b). Behavior of in situ human native adipose tissue CD34+ stromal/progenitor cells during different stages of repair. Tissue-resident CD34+ stromal cells as a source of myofibroblasts. Anat Rec 298, 917–930.CrossRefGoogle ScholarPubMed
Diaz-Flores, L., Gutierrez, R., Madrid, J.F., Varela, H., Valladares, F., Acosta, E., Martin-Vasallo, P. & Diaz-Flores, L. Jr. (2009). Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24, 909–969.Google Scholar
Díaz-Flores, L., Gutierrez, R. & Varela, H. (1994). Angiogenesis: An update. Histol Histopathol 9, 807–843.Google Scholar
Diss, A., Hitzig, C., Charbit, Y. & Salsou, B. (2003). Le point sur les facteurs de croissance dans la regeneration osseuse: Revue de literature. J Parodontol Implantol Orale 22, 5–19.Google Scholar
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D.J. & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315–317.Google Scholar
Dore-Duffy, P. & Cleary, K. (2011). Morphology and properties of pericytes. Methods Mol Biol 686, 49–68.Google Scholar
Duan, X., Tu, Q., Zhang, J., Ye, J., Sommer, C., Mostoslavsky, G., Kaplan, D., Yang, P. & Chen, J. (2011). Application of induced pluripotent stem (iPS) cells in periodontal tissue regeneration. J Cell Physiol 226(1), 150–157.CrossRefGoogle ScholarPubMed
Faussone-Pellegrini, M.S. & Popescu, L.M. (2011). Telocytes. Biomol Concepts 2, 481–489.Google Scholar
Feng, F., Akiyama, K., Liu, Y., Yamaza, T., Wang, T.M., Chen, J.H., Wang, B.B., Huang, G.T., Wang, S. & Shi, S. (2010). Utility of PDL progenitors for in vivo tissue regeneration: A report of 3 cases. Oral Dis 6, 20–28.Google Scholar
Fina, L., Molgaard, H.V., Robertson, D., Bradley, N.J., Monaghan, P., Delia, D., Sutherland, D.R., Baker, M.A. & Greaves, M.F. (1990). Expression of the CD34 gene in vascular endothelial cells. Blood 75, 2417–2426.CrossRefGoogle ScholarPubMed
Gherghiceanu, M. & Popescu, L.M. (2005). Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification. J Cell Mol Med 9, 893–910.Google Scholar
Gronthos, S., Mrozik, K., Shi, S. & Bartold, P.M. (2006). Ovine periodontal ligament stem cells: Isolation, characterization, and differentiation potential. Calcif Tissue Int 79, 310–317.Google Scholar
Haniffa, M.A., Collin, M.P., Buckley, C.D. & Dazzi, F. (2009). Mesenchymal stem cells: The fibroblasts’ new clothes? Haematologica 94, 258–263.Google Scholar
Hayat, M.A. (2000). Principles and Techniques of Electron Microscopy—Biological Applications, 4th ed. Cambridge, UK: Cambridge University Press.Google Scholar
Hürzeler, M.B. & Weng, D. (1999). A single-incision technique to harvest subepithelial connective tissue grafts from the palate. Int J Periodont Rest 19, 279–287.Google Scholar
Hynes, K., Menicanin, D., Gronthos, S. & Bartold, P.M. (2012). Clinical utility of stem cells for periodontal regeneration. Periodontol 2000 59, 203–227.Google Scholar
Karring, T., Nyman, S. & Lindhe, J. (1980). Healing following implantation of periodontitis affected roots into bone tissue. J Clin Periodontol 7, 96–105.Google Scholar
Kirkland, O. (1931). The suppurative periodontal pus pocket; its treatment by the modified flap operation. J Am Dent Assoc 18, 1462–1470.Google Scholar
Liao, J., Al Shahrani, M., Al-Habib, M., Tanaka, T. & Huang, G.T. (2011). Cells isolated from inflamed periapical tissue express mesenchymal stem cell markers and are highly osteogenic. J Endod 37, 1217–1224.Google Scholar
Lin, G., Garcia, M., Ning, H., Banie, L., Guo, Y.L., Lue, T.F. & Lin, C.S. (2008). Defining stem and progenitor cells within adipose tissue. Stem Cells Dev 17, 1053–1063.Google Scholar
Lin, C.S. & Lue, T.F. (2013). Defining vascular stem cells. Stem Cells Dev 22, 1018–1026.Google Scholar
Lin, C.S., Xin, Z.C., Dai, J. & Lue, T.F. (2013). Commonly used mesenchymal stem cell markers and tracking labels: Limitations and challenges. Histol Histopathol 28, 1109–1116.Google Scholar
Lin, C.S., Xin, Z.C., Deng, C.H., Ning, H., Lin, G. & Lue, T.F. (2010). Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol 25, 807–815.Google ScholarPubMed
Majesky, M.W., Dong, X.R., Hoglund, V., Mahoney, W.M. Jr. & Daum, G. (2011). The adventitia: A dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol 31, 1530–1539.Google Scholar
Majno, G. (1965). Ultrastructure of the vascular membrane. In Handbook of Physiology section 2, vol. III Hamilton, W.F., Dow, P. (Eds.), 2293–2375. Washington, DC: Amer Physiol Soc.Google Scholar
Maumus, M., Peyrafitte, J.A., D’angelo, R., Fournier-Wirth, C., Bouloumié, A., Casteilla, L., Sengenès, C. & Bourin, P. (2011). Native human adipose stromal cells: Localization, morphology and phenotype. Int J Obes (Lond) 35, 1141–1153.CrossRefGoogle ScholarPubMed
Mellonig, J.T. (2000). Human histologic evaluation of a bovine-derived bone xenograft in the treatment of periodontal osseous defects. Int J Periodontics Restorative Dent 20, 19–29.Google Scholar
Miller, P.D. Jr. (1985). A classification of marginal tissue recession. Int J Periodont Rest 5, 8–13.Google Scholar
Nielsen, J.S. & Mcnagny, K.M. (2008). Novel functions of the CD34 family. J Cell Sci 121, 3683–3692.Google Scholar
Ning, H., Lin, G., Lue, T.F. & Lin, C.S. (2006). Neuron-like differentiation of adipose tissue-derived stromal cells and vascular smooth muscle cells. Differentiation 74, 510–518.Google Scholar
Nyman, S., Karring, T., Lindhe, J. & Plantén, S. (1980). Healing following implantation of periodontitis-affected roots into gingival connective tissue. J Clin Periodontol 7, 394–401.Google Scholar
Paolantonio, M., Scarano, A., Di Placido, G., Tumini, V., D’Archivio, D. & Piattelli, A. (2001). Periodontal healing in humans using anorganic bovine bone and bovine peritoneum-derived collagen membrane: A clinical and histologic case report. Int J Periodontics Restorative Dent 21, 505–515.Google Scholar
Park, J.C., Kim, J.M., Jung, I.H., Kim, J.C., Choi, S.H., Cho, C.S. & Kim, C.S. (2011). Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: In vitro and in vivo evaluations. J Clin Periodontol 38, 721–731.CrossRefGoogle ScholarPubMed
Popescu, L.M. & Faussone-Pellegrini, M.S. (2010). Telocytes—a case of serendipity: The winding way from interstitial cells of Cajal (ICC), via interstitial Cajal-like cells (ICLC) to telocytes. J Cell Mol Med 14, 729–740.CrossRefGoogle Scholar
Pusztaszeri, M.P., Seelentag, W. & Bosman, F.T. (2006). Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem 54, 385–395.CrossRefGoogle ScholarPubMed
Regezi, J.A., Nickoloff, B.J. & Headington, J.T. (1992). Oral submucosal dendrocytes: Factor XIIIa+ and CD34+ dendritic cell populations in normal tissue and fibrovascular lesions. J Cutan Pathol 19, 398–406.Google Scholar
Roman, A., Câmpian, R., Domsa, I., Soanca, A. & Gocan, H. (2010). Subepithelial connective tissue graft for root coverage: Clinical case reports and histologic evaluation. Rom J Morphol Embryol 51, 3–6.Google ScholarPubMed
Roman, A., Soanca, A., Barbu-Tudoran, L., Irimie, A.I. & Pall, E. (2012). Comparative evaluation of the influence of two resin-based restorative materials on the behavior of progenitor-like cells. J Optoelectron Adv Mat 14, 491–496.Google Scholar
Roman, A., Soancă, A., Florea, A. & Páll, E. (2013). In vitro characterization of multipotent mesenchymal stromal cells isolated from palatal subepithelial tissue grafts. Microsc Microanal 19, 370–380.Google Scholar
Ronay, V., Belibasakis, G.N., Attin, T., Schmidlin, P.R. & Bostanci, N. (2014). Expression of embryonic stem cell markers and osteogenic differentiation potential in cells derived from periodontal granulation tissue. Cell Biol Int 38, 179–186.Google Scholar
Ronay, V., Belibasakis, G.N., Schmidlin, P.R. & Bostanci, N. (2013). Infected periodontal granulation tissue contains cells expressing embryonic stem cell markers. A pilot study. Schweiz Monatsschr Zahnmed 123, 12–16.Google ScholarPubMed
Ross, M.H., Kaye, G.J. & Pawlina, W. (2003). Histology a Textbook and Atlas, 4th ed. Baltimore, Philadelphia: Lippincott Williams and Wilkins.Google Scholar
Sartore, S., Chiavegato, A., Faggin, E., Franch, R., Puato, M., Ausoni, S. & Pauletto, P. (2001). Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: From innocent bystander to active participant. Circ Res 89, 1111–1121.Google Scholar
Seo, B.M., Miura, M., Gronthos, S., Bartold, P.M., Batouli, S., Brahim, J., Young, M., Robey, P.G., Wang, C.Y. & Shi, S. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364, 149–155.Google Scholar
Steiner, G.G., Francis, W., Burrell, R., Kallet, M.P., Steiner, D.M. & Macias, R. (2008). The healing socket and socket regeneration. Compend Contin Educ Dent 29, 114–116.Google Scholar
Stolzing, A., Bauer, E. & Scutt, A. (2012). Suspension cultures of bone-marrow-derived mesenchymal stem cells: Effects of donor age and glucose level. Stem Cells Dev 21, 2718–2723.Google Scholar
Suga, H., Matsumoto, D., Eto, H., Inoue, K., Aoi, N., Kato, H., Araki, J. & Yoshimura, K. (2009). Functional implications of CD34 expression in human adipose-derived stem/progenitor cells. Stem Cells Dev 18, 1201–1210.Google Scholar
Suster, S., Fisher, C. & Moran, C.A. (1998). Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. Am J Surg Pathol 22, 863–872.Google Scholar
Tonetti, M.S., Cortellini, P., Lang, N.P., Suvan, J.E., Adriaens, P., Dubravec, D., Fonzar, A., Fourmousis, I., Rasperini, G., Rossi, R., Silvestri, M., Topoll, H., Wallkamm, B. & Zybutz, M. (2004). Clinical outcomes following treatment of human intrabony defects with GTR/bone replacement material or access flap alone. A multicenter randomized controlled clinical trial. J Clin Periodontol 31(9), 770–776.Google Scholar
Trombelli, L., Heitz-Mayfield, L.J., Needleman, I., Moles, D. & Scabbia, A. (2002). A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol 29(Suppl 3), 17–35.Google Scholar
van de Rijn, M., Lombard, C.M. & Rouse, R.V. (1994). Expression of CD34 by solitary fibrous tumors of the pleura, mediastinum, and lung. Am J Surg Pathol 18, 814–820.Google Scholar
von Tell, D., Armulik, A. & Betsholtz, C. (2006). Pericytes and vascular stability. Exp Cell Res 312, 623–629.Google Scholar
Watt, I.M. (2003). The Principles and Practice of Electron Microscopy. Cambridge, UK: Cambridge University Press.Google Scholar
Weiss, S.W. & Nickoloff, B.J. (1993). CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 17, 1039–1045.CrossRefGoogle ScholarPubMed
Wennstrom, J.L., Heijl, L. & Lindhe, J. (2008). Periodontal surgery: Access therapy. In Clinical Periodontology and Implant Dentistry, 5th ed. Lindhe J., Lang N.P. & Karring T. (Eds.), pp. 783–822. Blackwell: Munksgaard.Google Scholar
Yamazaki, K. & Eyden, B.P. (1995). Ultrastructural and immunohistochemical observations on intralobular fibroblasts of human breast, with observations on the CD34 antigen. J Submicrosc Cytol Pathol 27, 309–323.Google Scholar
Yazid, F.B., Gnanasegaran, N., Kunasekaran, W., Govindasamy, V. & Musa, S. (2014). Comparison of immunodulatory properties of dental pulp stem cells derived from healthy and inflamed teeth. Clin Oral Investig 18, 2103–2112.Google Scholar
Yu, S., Diao, S., Wang, J., Ding, G., Yang, D. & Fan, Z. (2014). Comparative analysis of proliferation and differentiation potentials of stem cells from inflamed pulp of deciduous teeth and stem cells from exfoliated deciduous teeth. Biomed Res Int 2014, 930907.Google Scholar
Zengin, E., Chalajour, F., Gehling, U.M., Ito, W.D., Treede, H., Lauke, H., Weil, J., Reichenspurner, H., Kilic, N. & Ergun, S. (2006). Vascular wall resident progenitor cells: A source for postnatal vasculogenesis. Development 133, 1543–1551.Google Scholar
Zimmermann, K.W. (1923). Der feinere bau der blutcapillares. Z Anat Entwicklungsgesch 68, 3–109.Google Scholar
Zuk, P.A., Zhu, M., Ashijian, P., De Ugarte, D.A., Huang, J.I., Mizuno, H., Alfonso, Z.C., Fraser, J.K., Benhaim, P. & Hedrick, M.H. (2002). Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13, 4279–4295.Google Scholar