Generation of a Functional Liver Tissue Mimic Using Adipose Stromal Vascular Fraction Cell-derived Vasculatures

Overview

Journal Sci Rep

Specialty Science

Date 2013 Jul 6

PMID 23828203

Citations 28

Authors

S S Nunes

J G Maijub

L Krishnan

V M Ramakrishnan

L R Clayton

S K Williams

J B Hoying

N L Boyd

Affiliations

Soon will be listed here.

Abstract

One of the major challenges in cell implantation therapies is to promote integration of the microcirculation between the implanted cells and the host. We used adipose-derived stromal vascular fraction (SVF) cells to vascularize a human liver cell (HepG2) implant. We hypothesized that the SVF cells would form a functional microcirculation via vascular assembly and inosculation with the host vasculature. Initially, we assessed the extent and character of neovasculatures formed by freshly isolated and cultured SVF cells and found that freshly isolated cells have a higher vascularization potential. Generation of a 3D implant containing fresh SVF and HepG2 cells formed a tissue in which HepG2 cells were entwined with a network of microvessels. Implanted HepG2 cells sequestered labeled LDL delivered by systemic intravascular injection only in SVF-vascularized implants demonstrating that SVF cell-derived vasculatures can effectively integrate with host vessels and interface with parenchymal cells to form a functional tissue mimic.

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References

da Justa Pinheiro C, de Queiroz J, Guimaraes-Ferreira L, Vitzel K, Nachbar R, Oliveira de Sousa L . Local injections of adipose-derived mesenchymal stem cells modulate inflammation and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin-deficient skeletal muscle. Stem Cell Rev Rep. 2011; 8(2):363-74. DOI: 10.1007/s12015-011-9304-0. View

Boyd N, Nunes S, Jokinen J, Krishnan L, Chen Y, Smith K . Microvascular mural cell functionality of human embryonic stem cell-derived mesenchymal cells. Tissue Eng Part A. 2011; 17(11-12):1537-48. PMC: 3098949. DOI: 10.1089/ten.TEA.2010.0397. View

Gao Y, Hu H, Chen K . Primary porcine hepatocytes with portal vein serum cultured on microcarriers or in spheroidal aggregates. World J Gastroenterol. 2002; 6(3):365-370. PMC: 4688753. DOI: 10.3748/wjg.v6.i3.365. View

LeBlanc A, Touroo J, Hoying J, Williams S . Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction. Am J Physiol Heart Circ Physiol. 2011; 302(4):H973-82. PMC: 3322738. DOI: 10.1152/ajpheart.00735.2011. View

Cardinal K, Bonnema G, Hofer H, Barton J, Williams S . Tissue-engineered vascular grafts as in vitro blood vessel mimics for the evaluation of endothelialization of intravascular devices. Tissue Eng. 2007; 12(12):3431-8. DOI: 10.1089/ten.2006.12.3431. View

Stratman A, Malotte K, Mahan R, Davis M, Davis G . Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood. 2009; 114(24):5091-101. PMC: 2788982. DOI: 10.1182/blood-2009-05-222364. View

Chang C, Nunes S, Sibole S, Krishnan L, Williams S, Weiss J . Angiogenesis in a microvascular construct for transplantation depends on the method of chamber circulation. Tissue Eng Part A. 2009; 16(3):795-805. PMC: 2862615. DOI: 10.1089/ten.TEA.2009.0370. View

Abramsson A, Lindblom P, Betsholtz C . Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J Clin Invest. 2003; 112(8):1142-51. PMC: 213487. DOI: 10.1172/JCI18549. View

Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H . Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology. 2007; 45(5):1229-39. DOI: 10.1002/hep.21582. View

10.

Rupnick M, Panigrahy D, Zhang C, Dallabrida S, Lowell B, Langer R . Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci U S A. 2002; 99(16):10730-5. PMC: 125027. DOI: 10.1073/pnas.162349799. View

11.

Jain R . Molecular regulation of vessel maturation. Nat Med. 2003; 9(6):685-93. DOI: 10.1038/nm0603-685. View

12.

Carmona R, Gonzalez-Iriarte M, Macias D, Perez-Pomares J, Munoz-Chapuli R . Immunolocalization of the transcription factor Slug in the developing avian heart. Anat Embryol (Berl). 2000; 201(2):103-9. DOI: 10.1007/pl00008230. View

13.

Lammie A, Drobnjak M, Gerald W, Saad A, Cote R, Cordon-Cardo C . Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem. 1994; 42(11):1417-25. DOI: 10.1177/42.11.7523489. View

14.

Nagata H, Nishitai R, Shirota C, Zhang J, Koch C, Cai J . Prolonged survival of porcine hepatocytes in cynomolgus monkeys. Gastroenterology. 2007; 132(1):321-9. DOI: 10.1053/j.gastro.2006.10.013. View

15.

Cervelli V, Gentile P, De Angelis B, Calabrese C, Di Stefani A, Scioli M . Application of enhanced stromal vascular fraction and fat grafting mixed with PRP in post-traumatic lower extremity ulcers. Stem Cell Res. 2011; 6(2):103-11. DOI: 10.1016/j.scr.2010.11.003. View

16.

Eto H, Ishimine H, Kinoshita K, Watanabe-Susaki K, Kato H, Doi K . Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency. Stem Cells Dev. 2012; 22(6):985-97. PMC: 3585481. DOI: 10.1089/scd.2012.0442. View

17.

Boyd N, Nunes S, Krishnan L, Jokinen J, Ramakrishnan V, Bugg A . Dissecting the role of human embryonic stem cell-derived mesenchymal cells in human umbilical vein endothelial cell network stabilization in three-dimensional environments. Tissue Eng Part A. 2012; 19(1-2):211-23. PMC: 3530951. DOI: 10.1089/ten.tea.2011.0408. View

18.

Mizuno H, Tobita M, Uysal A . Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells. 2012; 30(5):804-10. DOI: 10.1002/stem.1076. View

19.

Gimble J, Bunnell B, Chiu E, Guilak F . Concise review: Adipose-derived stromal vascular fraction cells and stem cells: let's not get lost in translation. Stem Cells. 2011; 29(5):749-54. DOI: 10.1002/stem.629. View

20.

Knowles B, HOWE C, Aden D . Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980; 209(4455):497-9. DOI: 10.1126/science.6248960. View