Effect of Whole Bone Marrow Cell Infusion in the Progression of Experimental Chronic Renal Failure

Caldas, Heloisa Cristina; Fernandes, Ida Maria Maximina; Gerbi, F.; Souza, Ana Carolina C. Pessoa de; Baptista, Maria Alice Sperto Ferreira; Ramalho, Horácio José; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Pavarino, Érika Cristina; Braile, Domingo Marcolino; Abbud-Filho, Mário

doi:10.1016/j.transproceed.2008.03.009

Cited by 43 publications

(41 citation statements)

References 6 publications

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“…1 MSCs treatment has also been tested in native chronic kidney disease models. In a 5/6 nephrectomy model, allogeneic MSCs injection decreased proteinuria and fibrosis [6][7][8] when intravenously injected or under the renal capsule, while the comparison between bone marrow mononuclear cells (BMCs) and MSCs injected in the renal parenchyma showed a better outcome with BMC cell therapy [9]. In a Col4A3 knock-out chronic model, syngeneic MSCs were able to reduce interstitial fibrosis [10], while allogeneic MSCs did not ameliorate the progression of the disease [11].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

Franquesa

Herrero

Torras

et al. 2012

Stem Cells and Development

123

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In solid organ transplantation, mesenchymal stem cell (MSC) therapy is strongly emerging among other cell therapies due to the positive results obtained in vitro and in vivo as an immunomodulatory agent and their potential regenerative role. We aimed at testing whether a single dose of MSCs, injected at 11 weeks after kidney transplantation for the prevention of chronic mechanisms, enhanced regeneration and provided protection against the inflammatory and fibrotic processes that finally lead to the characteristic features of chronic allograft nephropathy (CAN). Either bone marrow mononuclear cells (BMCs) injection or no-therapy (NT) were used as control treatments. A rat kidney transplantation model of CAN with 2.5 h of cold ischemia was used, and functional, histological, and molecular parameters were assessed at 12 and 24 weeks after transplantation. MSC and BMC cell therapy preserves renal function at 24 weeks and abrogates proteinuria, which is typical of this model (NT24w: 68.9 -26.5 mg/24 h, MSC24w: 16.6 -2.3 mg/24 h, BMC24w: 24.1 -5.3 mg/24 h, P < 0.03). Only MSC-treated animals showed a reduction in interstitial fibrosis and tubular atrophy (NT24w: 2.3 -0.29, MSC24w: 0.4 -0.2, P < 0.03), less T cells (NT: 39.6 -9.5, MSC: 8.1 -0.9, P < 0.03) and macrophages (NT: 20.9 -4.7, MSC: 5.9 -1.7, P < 0.05) infiltrating the parenchyma and lowered expression of inflammatory cytokines while increasing the expression of anti-inflammatory factors. MSCs appear to serve as a protection from injury development rather than regenerate the damaged tissue, as no differences were observed in Ki67 expression, and kidney injury molecule-1, Clusterin, NGAL, and hepatocyte growth factor expression were only up-regulated in nontreated animals. Considering the results, a single delayed MSC injection is effective for the long-term protection of kidney allografts.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

Franquesa

Herrero

Torras

et al. 2012

Stem Cells and Development

123

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“…Implantation of stem/progenitor cells can be principally performed by infusion via the blood vessel system [8,9] or by punctual implantation into the diseased parenchyma of the kidney [10,11]. An alternative approach is to implant them in the space left between the organ capsule and the outer parenchyma at the earlier site of nephron formation [12].…”

Section: Introductionmentioning

confidence: 99%

Initial steps to stabilize the microenvironment for implantation of stem/progenitor cells in diseased renal parenchyma

Minuth

Denk²

2013

Transplant Technol

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Stem/progenitor cells are in the focus of research as a therapeutic perspective to cure acute and chronic renal failure. Following this innovative strategy one has to consider that stem/progenitor cells are first kept in the beneficial atmosphere of a CO 2 -dependent culture medium, while after implantation they are exposed to unbalanced interstitial fluid of diseased parenchyma. However, this abrupt transition has consequences, since it limits survival of implanted stem/progenitor cells. To offer a constant environment during isolation, culture, surgical processing and initial seeding within diseased parenchyma, an improved concept is under current work. In present experiments stabilization of fluid environment was investigated by isolating renal stem/progenitor cells in chemically defined and CO 2 -stabilized culture media. Interstitial influences on spatial development of tubules were tested by mounting stem/progenitor cells in a polyester fleece as a substitute for extracellular matrix and by transporting always fresh medium in perfusion culture for 13 days. Finally, morphological quality of raised constructs was analyzed by histochemistry, light and transmission electron microscopy. The present results demonstrate that three different culture media can be short-listed for protecting stem/progenitor cells during the process of implantation. Earlier approved Iscove´s Modified Dulbecco´s Medium buffered by HEPES revealed formation of numerous tubules. Also application of Leibovitz's L-15 Medium and CO 2 Independent Medium demonstrated unexpected promoting effects on the generation of tubules. In all series typical features of transporting tubule cells were registered. Formation of an excess of vacuoles as an indicator for cytotoxicity was not observed. In conclusion, although very different in chemical composition the tested culture media reflect an advantageous microenvironment for isolation, implantation and development of stem/ progenitor cells.

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“…In this concern, Lin et al mentioned that MSC can be used in therapy of fibrotic diseases [35] . Other researchers indicated that whole bone marrow-derived cells have been shown to be effective in treating fibrosis development [36,37] . Furthermore, MSC therapies were tested for heart, lung, and chronic diseases and were found to be effective at reducing the fibrotic area and correlated with good outcomes [38] .…”

Section: Discussionmentioning

confidence: 99%

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

Sakr

Rashed

Zarouk

et al. 2013

Asian Pacific Journal of Tropical Biomedicine

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Effect of Whole Bone Marrow Cell Infusion in the Progression of Experimental Chronic Renal Failure

Cited by 43 publications

References 6 publications

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

Initial steps to stabilize the microenvironment for implantation of stem/progenitor cells in diseased renal parenchyma

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

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