期刊论文详细信息
Lipids in Health and Disease
Organ specific regenerative markers in peri-organ adipose: kidney
John W Ludlow1  Timothy Bertram1  Deepak Jain1  Roger M Ilagan1  Rusty Kelley1  Kelly I Guthrie1  Sarah F Quinlan1  Namrata Sangha1  Christopher W Genheimer1  Joydeep Basu1 
[1] Bioprocess Research and Assay Development, Tengion Inc, 3929 Westpoint Blvd., Suite G, Winston-Salem, NC 27103, USA
关键词: cell therapy;    tissue engineering;    regenerative medicine;    WT1;    VEGF;    chronic kidney disease;    kidney;    adipose;    EPO;    erythropoietin;   
Others  :  1212494
DOI  :  10.1186/1476-511X-10-171
 received in 2011-08-23, accepted in 2011-09-29,  发布年份 2011
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【 摘 要 】

Background

Therapeutically bioactive cell populations are currently understood to promote regenerative outcomes in vivo by leveraging mechanisms of action including secretion of growth factors, site specific engraftment and directed differentiation. Constitutive cellular populations undoubtedly participate in the regenerative process. Adipose tissue represents a source of therapeutically bioactive cell populations. The potential of these cells to participate in various aspects of the regenerative process has been demonstrated broadly. However, organ association of secretory and developmental markers to specific peri-organ adipose depots has not been investigated. To characterize this topographical association, we explored the potential of cells isolated from the stromal vascular fraction (SVF) of kidney sourced adipose to express key renal associated factors.

Results

We report that renal adipose tissue is a novel reservoir for EPO expressing cells. Kidney sourced adipose stromal cells demonstrate hypoxia regulated expression of EPO and VEGF transcripts. Using iso-electric focusing, we demonstrate that kidney and non-kidney sourced adipose stromal cells present unique patterns of EPO post-translational modification, consistent with the idea that renal and non-renal sources are functionally distinct adipose depots. In addition, kidney sourced adipose stromal cells specifically express the key renal developmental transcription factor WT1.

Conclusions

Taken together, these data are consistent with the notion that kidney sourced adipose stromal (KiSAS) cells may be primed to recreate a regenerative micro-environment within the kidney. These findings open the possibility of isolating solid-organ associated adipose derived cell populations for therapeutic applications in organ-specific regenerative medicine products.

【 授权许可】

   
2011 Basu et al; licensee BioMed Central Ltd.

【 预 览 】
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【 参考文献 】
  • [1]Crisan M, Solomon Y, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schuger R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B: A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008, 3:301-313.
  • [2]da Silva Meirelles L, Chagastelles PC, Nardi NB: Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006, 119:2204-2213.
  • [3]Lin G, Garcia M, Ning H, Banie L, Guo YL, Lue TF, Lin CS: Defining stem and progenitor populations within adipose tissue. Stem Cells Dev 2008, 17:1053-1063.
  • [4]Basu J, Genheimer C, Guthrie KI, Sangha N, Quinlan SF, Bruce AT, Reavis B, Halberstadt C, Ilagan RM, Ludlow JW: Expansion of the human adipose derived stromal vascular cell fraction yields a population of smooth muscle-like cells with markedly distinct phenotypic and functional properties relative to mesenchymal stem cells. Tissue Eng Part C 2011, 17:843-860.
  • [5]Basu J, Ludlow JW: Platform technologies for tubular organ regeneration. Trends Biotechnol 2010, 28:526-533.
  • [6]Bjorndal B, Burri L, Staalesen V, Skorve J, Berge RK: Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes 2011. 490650
  • [7]Cook A, Cowan C: Adipose. Stembook 2009.
  • [8]Roca-Rivada A, Alonso J, Al-Massadi O, Castelao C, Peinado JR, Seone LM, Casanueva FF, Pardo M: Secretome analysis of rat adipose tissue shows location specific roles for each depot type. J Proteomics 2011, 74:1068-1079.
  • [9]Caesar R, Manieri M, Kelder T, Boekschoten M, Evelo C, Muller M, Kooistra K, Cinti S, Kleeman R, Drevon CA: A combined transcriptomics and lipidomics analysis of subcutaneous, epididymal and mesenteric adipose tissue reveals marked functional differences. Plos One 2010, e11525.
  • [10]Levi B, James AW, Glotzbach JP, Wan DC, Commons GW, Longaker MT: Depot specific variation in the osteogenic and adipogenic potential of human adipose derived stromal cells. Plast Reconstr Surg 2010, 126:822-834.
  • [11]Schipper BM, Marra KG, Zhang W, Donnenberg AD, Rubin JP: Regional anatomic and age effects on cell function of human adipose derived stem cells. Ann Plast Surg 2008, 60:538-544.
  • [12]Basu J, Genheimer CW, Rivera EA, Payne R, Mihalko K, Guthrie K, Bruce AT, Robbins N, McCoy D, Sangha N, Ilagan R, Knight T, Spencer T, Wagner B, Jayo MJ, Jain D, Ludlow JW, Halberstadt C: Functional evaluation of primary renal cell/biomaterial Neo-Kidney Augment prototypes for renal tissue engineering. Cell Transplant 2011.
  • [13]Spector DL: Cells, a laboratory manual. Cold Spring Harbor Press 1997.
  • [14]Sytkowski AJ: Erythropoietin. Blood, brain and beyond. Wiley 2004.
  • [15]Gleadle JM: How cells sense oxygen: Lessons from and for the kidney. Nephrology 2006, 14:86-93.
  • [16]Ueda S, Yamagishi S, Matsumoto Y, Kaida Y, Fujimi-Hayashida A, Koike K, Tanaka H, Fukami K, Okuda S: Involvement of asymmetric dimethylarginine (ADMA) in glomerular capillary loss and sclerosis in a rat model of chronic kidney disease (CKD). Life Sci 2009, 84:853-856.
  • [17]Lasne F, de Ceaurriz J: Recombinant erythropoietin in urine. Nature 2000, 405:635.
  • [18]Bodo E, Kromminga A, Funk W, Laugsch M, Duske U, Jelkmann W, Paus R: Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin. FASEB J 2007, 21:3346-3354.
  • [19]Weidemann A, Johnson RS: Nonrenal regulation of EPO synthesis. Kidney Int 2009, 75:682-688.
  • [20]Lee K, Min BG, Mun CH, Lee SR, Won YS: Pulse push/pull hemodialysis in a canine renal failure model. Blood Purif 2008, 26:491-497.
  • [21]Roberts SG: Transcriptional regulation by WT1 in development. Curr Opin Genet Dev 2005, 15:542-547.
  • [22]Litbarg NO, Gudehithlu KP, Sethupathi P, Arruda JA, Dunea G, Singh AK: Activated omentum becomes rich in factors that promote healing and tissue regeneration. Cell Tissue Res 2007, 328:487-497.
  • [23]Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT: Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 2008, 454:109-113.
  • [24]Hammes A, Guo JK, Lutsch G, Leheste JR, Landrock D, Ziegler U, Gubler MC, Schedl A: Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell 2001, 106:319-329.
  • [25]Niksic M, Slight J, Sanford JR, Caceres JF, Hastie ND: The Wilms' tumor protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Gen 2004, 13:463-471.
  • [26]Hopkins C, Li J, Rae F, Little MH: Stem cell options for kidney disease. J Pathol 2009, 217:265-281.
  • [27]Sagrinati C, Ronconi R, Lazzeri E, Lasagni L, Romagnani P: Stem cell approaches for kidney repair: choosing the right cells. Trends Mol Med 2008, 14:277-285.
  • [28]Caplan AI: Why are MSCs therapeutic? New data:new insight. J Pathol 2009, 217:318-324.
  • [29]Kloting N, Berthold S, Kovacs P, Schon MR, Fasshauer , Ruschke K, Sturmvoll M, Bluher M: MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One 2009, 4:e4699.
  • [30]Belanger C, Hould FS, Lebel S, Biron S, Brochu G, Tchernof A: Omental and subcutaneous adipose tissue steroid levels in obese men. Steroids 2006, 71:674-682.
  • [31]Cinti S: Transdifferentiation properties of adipocytes in the Adipose Organ. Am J Physiol Endocrinol Metab 2009. PMID 19458063
  • [32]Fandrey J: Oxygen-dependant and tissue-specific regulation of erythropoietin gene expression. Am J Physiol Regul Integr Comp Physiol 2004, 286:R977-R988.
  • [33]Bachmann S, Le Hir M, Eckardt KU: Co-localization of mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem Cytochem 1993, 41:335-341.
  • [34]Maxwell PH, Osmond MK, Pugh CW, Hervet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ: Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 1993, 44:1149-1162.
  • [35]Aboushwareb T, Egydio F, Straker L, Gyabaah K, Atala A, Yoo JJ: Erythropoietin producing cells for potential cell therapy. World J Urol 2008, 26:295-300.
  • [36]Triolo G, Canavese C, Di Giuolio S: Reasons for producing guidelines on anemia of chronic renal failure: dialysis outcome quality initiative of the National Kidney Foundation. Int J Artif Organs 1998, 21:751-756.
  • [37]Tamilvanan S, Raja NL, Sa B, Basu SK: Clinical concerns of immunogenicity produced at cellular levels by biopharmaceuticals following their parenteral administration into human body. J Drug Target 2010, 18:489-498.
  • [38]Novak JE, Szczech LA: Triumph and tragedy: anemia management in chronic kidney disease. Curr Opin Nephrol Hypertens 2008, 17:580-588.
  • [39]Bahlmann FH, Kielstein JT, Haller H, Fliser D: Erythropoietin and progression of CKD. Kidney Int 2007, 72:521-525.
  • [40]Campeau PM, Rafei M, Francois M, Birman E, Forner KA, Galipeau J: Mesenchymal stromal cells engineered to express erythropoietin induce anti-erythropoietin antibodies and anemia in allorecipients. Mol Ther 2009, 17:369-372.
  • [41]Togel F, Weiss K, Yang Y, Hu Z, Zhang P, Westenfelder C: Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol 2007, 292:1626-1635.
  • [42]Aydin Z, Duijs J, Bajema IM, van Zonneveld AJ, Rabelink TJ: Erythropoietin, progenitors and repair. Kidney Int Suppl 2007, 107:S16-S20.
  • [43]Sasaki R: Pleiotropic functions of erythropoietin. Intern Med 2003, 42:142-149.
  • [44]Plotkin MD, Goligorsky MS: Mesenchymal cells from adult kidney support angiogenesis and differentiate into multiple interstitial cell types including erythropoietin producing fibroblasts. Am J Physiol Renal Physiol 2006, 291:902-912.
  • [45]Lasne F, Martin L, Martin JA, de Ceaurriz J: Isoelectric profiles of human erythroipoietin are different in serum and urine. Int J Biol Macromol 2007, 41:354-357.
  • [46]Jenkins MA, Munch LC: Laparoscopic excision of a solitary renal cell carcinoma metastasis to the contralateral perirenal adipose tissue. Urology 2002, 59:444.
  • [47]Genheimer CW, Guthrie KI, Sholes JE, Bruce AT, Quinlan SF, Sangha N, Ilagan RM, Basu J, Burnette T, Ludlow JW: Increased urothelial cell detection in the primary bladder smooth muscle cell cultures with dual MACS/q-RT-PCR approach. Appl Immunohistochem Mol Morphol 2011, 19:184-189.
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