Abstract
In addition to its well-recognised impact on the immune system, HIV-1 infection has long been associated with disorders of other tissue types, and with the advent of long term anti-retroviral therapy specific toxicities of both bone and lipid tissues have emerged. These issues are of significant clinical importance in a population receiving life-time therapy. The mechanisms underpinning these toxicities have yet to be fully understood, and the relative contribution of virus and treatment (especially in the case of bone toxicities) fully elucidated.
Mesenchymal stem cells (MSCs) are pluripotent cells that can differentiate into cells, amongst others, of osteoblast and adipocyte lineage. They are largely resident in the bone marrow – although mesenchymal/stromal precursor cell ‘pools’ can be found in other tissues including adipose tissue. Increasingly MSCs are considered to play an important role in tissue homeostasis, repair and response to injury. In addition to their roles as bone/fat progenitor cells, they can also express receptors which could allow their infection by HIV-1. This chapter will deal with the prevalence of HIV-1 associated toxicities of lipid and bone, and treat of the existing evidence for a role for MSCs in the pathogenesis of these phenomena.
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Avram MM, Avram AS, James WD (2007) Subcutaneous fat in normal and diseased states 3. Adipogenesis: from stem cell to fat cell. J Am Acad Dermatol 56:472–492
Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH (2009) Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 57:1192–1203
Brown TT, Qaqish RB (2006) Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 20:2165–2174
Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650
Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347
Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084
Caron-Debarle M, Lagathu C, Boccara F, Vigouroux C, Capeau J (2010) HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med 16:218–229
Carr A (2007) Treatment strategies for HIV lipodystrophy. Curr Opin HIV AIDS 2:332–338
Carr A, Miller J, Eisman JA, Cooper DA (2001) Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre- antiretroviral therapy. AIDS 15:703–709
Cheng Z, Ou L, Zhou X, Li F, Jia X, Zhang Y, Liu X, Li Y, Ward CA, Melo LG, Kong D (2008) Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 16:571–579
Cotter EJ, Malizia AP, Chew N, Powderly WG, Doran PP (2007) HIV proteins regulate bone marker secretion and transcription factor activity in cultured human osteoblasts with consequent potential implications for osteoblast function and development. AIDS Res Hum Retroviruses 23:1521–1530
Cotter EJ, Ip HS, Powderly WG, Doran PP (2008) Mechanism of HIV protein induced modulation of mesenchymal stem cell osteogenic differentiation. BMC Musculoskelet Disord 9:33
Cotter EJ, Doran PP, Powderly WG (2009a) Progenitor cell types in HIV-1 infection: bioactivity and emerging targets for treatment. Curr HIV Res 7:508–518
Cotter EJ, Mallon PW, Doran PP (2009b) Is PPAR gamma a prospective player in HIV-1-associated bone disease? PPAR Res 2009:421376
Cotter EJ, Chew N, Powderly WG, Doran PP (2011) HIV type 1 alters mesenchymal stem cell differentiation potential and cell phenotype ex vivo. AIDS Res Hum Retroviruses 27:187–199
Feeney ER, Mallon PW (2011) HIV and HAART-associated dyslipidemia. Open Cardiovasc Med J 5:49–63
Gibellini D, de Crignis E, Ponti C, Cimatti L, Borderi M, Tschon M, Giardino R, Re MC (2008) HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation. J Med Virol 80:1507–1514
Gibellini D, Alviano F, Miserocchi A, Tazzari PL, Ricci F, Clo A, Morini S, Borderi M, Viale P, Pasquinelli G, Pagliaro P, Bagnara GP, Re MC (2011) HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells. Retrovirology 8:40
Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME (2006) Playing with bone and fat. J Cell Biochem 98:251–266
Jain RG, Lenhard JM (2002) Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J Biol Chem 277:19247–19250
Keruly JC, Chaisson RE, Moore RD (2001) Increasing incidence of avascular necrosis of the hip in HIV-infected patients. J Acquir Immune Defic Syndr 28:101–102
Lagathu C, Caron-Debarle M, Capeau J (2010) HIV protease inhibitors selectively inhibit osteoblast differentiation and induce premature senescence in human bone marrow mesenchymal stem cells. Antivir Ther 15:A11–A12
Lee CI, Cowan MJ, Kohn DB, Tarantal AF (2004) Simian immunodeficiency virus infection of hematopoietic stem cells and bone marrow stromal cells. J Acquir Immune Defic Syndr 36:553–561
Mallon PW, Miller J, Cooper DA, Carr A (2003) Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. AIDS 17:971–979
Mansilla E, Diaz Aquino V, Zambon D, Marin GH, Martire K, Roque G, Ichim T, Riordan NH, Patel A, Sturla F, Larsen G, Spretz R, Nunez L, Soratti C, Ibar R, Van Leeuwen M, Tau JM, Drago H, Maceira A (2011) Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes? Stem Cells Int 2011:943216
McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, Aldrovandi GM, Cardoso SW, Santana JL, Brown TT (2010) Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis 51:937–946
Moore AL, Vashisht A, Sabin CA, Mocroft A, Madge S, Phillips AN, Studd JW, Johnson MA (2001) Reduced bone mineral density in HIV-positive individuals. AIDS 15:1731–1733
Richardson J, Hill AM, Johnston CJ, McGregor A, Norrish AR, Eastwood D, Lavy CB (2008) Fracture healing in HIV-positive populations. J Bone Joint Surg Br 90:988–994
Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, Zhao L, Nagy TR, Peng X, Hu J, Feng X, van Hul W, Wan M, Cao X (2009) TGF-beta1- induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15:757–765
Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum SL, Yarasheski KE (2000) Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 14:F63–F67
Triant VA, Brown TT, Lee H, Grinspoon SK (2008) Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 93:3499–3504
Troll JG (2011) Approach to dyslipidemia, lipodystrophy, and cardiovascular risk in patients with HIV infection. Curr Atheroscler Rep 13:51–56
Tsekes G, Chrysos G, Douskas G, Paraskeva D, Mangafas N, Giannakopoulos D, Papanikolaou M, Georgiou E, Lazanas MC (2002) Body composition changes in protease inhibitor-naive HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors. HIV Med 3:85–90
Verma S, Rajaratnam JH, Denton J, Hoyland JA, Byers RJ (2002) Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol 55:693–698
Wang L, Mondal D, la Russa VF, Agrawal KC (2002) Suppression of clonogenic potential of human bone marrow mesenchymal stem cells by HIV type 1: putative role of HIV type 1 tat protein and inflammatory cytokines. AIDS Res Hum Retroviruses 18:917–931
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Cotter, E.J., Maughan, R.T., Doran, P.P. (2012). Role of Mesenchymal Stem Cells (MSC) in HIV-1 Associated Bone and Lipid Toxicities. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 8. Stem Cells and Cancer Stem Cells, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4798-2_8
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DOI: https://doi.org/10.1007/978-94-007-4798-2_8
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