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Stromal cells cultured from omentum express pluripotent markers, produce high amounts of VEGF, and engraft to injured sites

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Abstract

When rat omentum becomes activated by intraperitoneal injection of inert polydextran particles, these particles are rapidly surrounded by cells that express markers of adult stem cells (SDF–1α, CXCR4, WT–1) and of embryonic pluripotent cells (Oct–4, Nanog, SSEA–1). We have cultured such cells, because they may offer a convenient source of adult stem cells, and have found that they retain stem cell markers and produce high levels of vascular endothelial growth factor for up to ten passages. After systemic or local injection of these cultured cells into rats with acute injury of various organs, the cells specifically engraft at the injured sites. Thus, our experiments show that omental stromal cells can be cultured from activated omentum, and that these cells exhibit stem cell properties enabling them to be used for repair and possibly for the regeneration of damaged tissues.

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References

  • Andrews PW, Matin MM, Bahrami AR, Damjanov I, Gokhale P, Draper JS (2005) Embryonic stem (ES) cells and embryonal carcinoma (EC) cells. Opposite sides of the same coin. Biochem Soc Trans 33:1526–1530

    Article  PubMed  CAS  Google Scholar 

  • Cannaday JE (1948) Some uses of undetached omentum in surgery. Am J Surg 76:502–505

    Article  Google Scholar 

  • Chambers I, Smith A (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23:7150–7160

    Article  PubMed  CAS  Google Scholar 

  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 13:643–655

    Article  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  • Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic β-cells are formed by self-duplication rather then stem-cell differentiation. Nature 429:41–46

    Article  PubMed  CAS  Google Scholar 

  • Fatima B, Pinho M, Hurtado SP, El-Cheikh MC, Borojevic R (2005) Hematopoietic progenitors in the adult mouse omentum: permanent production of B lymphocytes and monocytes. Cell Tissue Res 319:91–102

    Article  Google Scholar 

  • Goldsmith HS (1994) Brain and spinal cord revascularization by omental transposition. Neurol Res 16:159–162

    PubMed  CAS  Google Scholar 

  • Goldsmith HS (1997) Omental transposition to the brain for Alzheimer’s disease. Ann N Y Acad Sci 826:323–336

    Article  PubMed  CAS  Google Scholar 

  • Goldsmith HS (2004) The evolution of omentum transposition: from lymphedema to spinal cord, stroke and Alzheimer’s disease. Neurol Res 26:586–593

    Article  PubMed  Google Scholar 

  • Gerrard L, Zhao D, Clark AJ, Cui W (2005) Stably transfected human embryonic stem cell clones express OCT–4 specific green fluorescent protein and maintain self-renewal and pluripotency. Stem Cells 23:124–133

    Article  PubMed  CAS  Google Scholar 

  • Grove JE, Bruscia E, Krause DS (2004) Plasticity of bone marrow-derived stem cells. Stem Cells 22:487–500

    Article  PubMed  Google Scholar 

  • Gudehithlu KP, Ahmed N, Yu H, Litbarg NO, Garber SL, Arruda JAL, Dunea G, Singh AK (2005) Antagonism of VEGF results in microvessel attrition and disorganization of wound tissue. J Lab Clin Med 145:194–203

    Article  PubMed  CAS  Google Scholar 

  • Hatano S-Y, Tada M, Kimura H, Shinpei Y, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T (2005) Pluripotency competence of cells associated with Nanog activity. Mech Dev 122:67–79

    Article  PubMed  CAS  Google Scholar 

  • Hatch HM, Zheng D, Jorgensen ML, Petersen BE (2002) SDF–1α/CXCR–4: a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured livers in rats. Cloning Stem Cells 4:339–351

    Article  PubMed  CAS  Google Scholar 

  • Hoffman R, Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P (2005) Hematology: basic principals and practice, 4th edn. Churchill-Livingston, Philadelphia

    Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzales XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg S, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    Article  PubMed  CAS  Google Scholar 

  • Kayali AG, Gunst KV, Campbell IL, Stotland A, Kritzik M, Guoxun L, Flodstrom-Tullberg M, Zhang Y-Q, Sarvetnick N (2003) The stromal cell-derived factor-1α (SDF–1α)/CXCR–4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas. J Cell Biol 163:859–869

    Article  PubMed  CAS  Google Scholar 

  • Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Massironi SMG, Periera LV, Caplan AI, Cerruti HF (2006) Isolation and characterization of a population of immature dental pulp stem cells expressing Oct–4 and other embryonic stem cell markers. Cell Tissue Organs 184:105–116

    Article  CAS  Google Scholar 

  • Kreisberg JL, Hoover RL, Karnovsky MJ (1978) Isolation and characterization of rat glomerular epithelial cells in vitro. Kidney Int 14:21–30

    Article  PubMed  CAS  Google Scholar 

  • Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT–1 is required for early kidney development. Cell 74:679–691

    Article  PubMed  CAS  Google Scholar 

  • Kuwana M, OkazakiY, Kodama H, Izumi K, Yasuoka H, Ogawa Y, Kawakami Y, Ikeda Y (2003) Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation. J Leukoc Biol 74:833–845

    Article  PubMed  CAS  Google Scholar 

  • Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ (2006) Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/SCID mice. Proc Natl Acad Sci USA 103:17438–17443

    Article  PubMed  CAS  Google Scholar 

  • Liebermann-Meffert D (2000) The greater omentum: anatomy, embryology, and surgical applications. Surg Clin North Am 80: 275–293

    Article  PubMed  CAS  Google Scholar 

  • Litbarg NO, Gudehithlu KP, Sethupathi P, Arruda JAL, Dunea G, Singh AK (2007) Activated omentum becomes rich in factors that promote healing and tissue regeneration. Cell Tissue Res 328:487–497

    Article  PubMed  CAS  Google Scholar 

  • Lu F-Z, Fujino M, Kitazawa Y, Uyama T, Hara Y, Funeshima N, Jiang J-Y, Umezawa A, Li X-K (2005) Characterization and gene transfer in mesenchymal stem cells derived from human umbilical-cord blood. J Lab Clin Med 146:271–278

    Article  PubMed  CAS  Google Scholar 

  • Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q (2004) The renal papilla is a niche for adult kidney stem cells. J Clin Invest 114:795–804

    PubMed  CAS  Google Scholar 

  • Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y (2001) Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104:233–245

    Article  PubMed  CAS  Google Scholar 

  • Park KM, Chen M, Bonventre JV (2001) Prevention of kidney/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem 276:11870–11876

    Article  PubMed  CAS  Google Scholar 

  • Peled A, Petit I, Kollet O, Magid M, Popomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lidor O, Alon R, Zipori D, Lapidot T (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845–848

    Article  PubMed  CAS  Google Scholar 

  • Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D (1990) The candidate Wilms’ tumor gene is involved in genitourinary development. Nature 346:194–197

    Article  PubMed  CAS  Google Scholar 

  • Ruhne M, Ungefroren H, Nussler A, Martin F, Brulport M, Schormann W, Hengstler JG, Klapper W, Ulrichs K, Hutchinson JA, Soria B, Parwaresch RM, Heeckt P, Kremer B, Fandrich F (2005) Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128:1774–1786

    Article  Google Scholar 

  • Sam R, Wanna L, Gudehithlu KP, Garber S, Dunea G, Arruda JAL, Singh AK (2006) Glomerular epithelial cells transform to myofibroblasts: early but not late removal of TGF-β reverses transformation. Transl Res 148:142–148

    Article  PubMed  CAS  Google Scholar 

  • Singh AK, Gudehithlu KP, Pegoraro AA, Singh GK, Basheerudin K, Robey RB, Arruda JAL, Dunea G (2004) Vascular factors in glucose treated mesangial cells and diabetic glomeruli. Changes in vascular factors impair endothelial cell growth and matrix. Lab Invest 84:597–606

    Article  PubMed  CAS  Google Scholar 

  • Singh AK, Gudehithlu KP, Litbarg, N, Sethupathi P, Arruda JAL, Dunea G (2007a) Transplanting fragments of diabetic pancreas into activated omentum gives rise to new insulin producing cells. Biochem Biophys Res Commun 355:258–262

    Article  CAS  Google Scholar 

  • Singh AK, Gudehithlu KP, Patri S, Litbarg N, Sethupathi P, Arruda JAL, Dunea G (2007b) Impaired integration of endothelial progenitor cells in capillaries of diabetic wounds is reversible with VEGF infusion. Transl Res 149:282–291

    Article  CAS  Google Scholar 

  • Solter D, Knowles BB (1978) Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA–1). Proc Natl Acad Sci USA 75:5565–5569

    Article  PubMed  CAS  Google Scholar 

  • Sudo K, Kanno M, Miharada Ogawa S, Hiroyama T, Saijo K, Nakamura Y (2007) Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adipogenic cells in vitro are present in most primary fibroblast-like populations. Stem Cells 25:1610–1617

    Article  PubMed  CAS  Google Scholar 

  • Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461

    Article  PubMed  CAS  Google Scholar 

  • Togel F, HuZ, Weiss K, Isaac J, Lange C, Westenfelder C (2005) Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Renal Physiol 289:F31–F42

    Article  Google Scholar 

  • Vernik J, Singh AK (2007) Omentum: power to heal and regenerate. Int J Artif Organs 30:95–99

    PubMed  CAS  Google Scholar 

  • Zhao Y, Huang Z, Lazzarini P, Wang Y, Di A, Chen M (2007) A unique human blood-derived cell population displays high potential for producing insulin. Biochem Biophys Res Commun 360:205–211

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Ms. Linda Wanna for culture work and Dr. Lev Rappoport for help with histological processing and immunostaining of tissues.

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Correspondence to Ashok K. Singh.

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Singh, A.K., Patel, J., Litbarg, N.O. et al. Stromal cells cultured from omentum express pluripotent markers, produce high amounts of VEGF, and engraft to injured sites. Cell Tissue Res 332, 81–88 (2008). https://doi.org/10.1007/s00441-007-0560-x

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  • DOI: https://doi.org/10.1007/s00441-007-0560-x

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