Embryonic Stem Cell Derived and Adult Hematopoietic Stem Cell Transplantation for Tolerance Induction in a Renal Allograft Recipient:—A Case Report

Trivedi, Hargovind L; Mishra, V V; Vanikar, Aruna V; Modi, Pranjal; Shah, Veena R; Shah, PR; Firoz, Ahad

doi:10.1016/j.transproceed.2006.08.173

Cited by 14 publications

(8 citation statements)

References 14 publications

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“…In addition, cases of COT with follow-up shorter than 1 year 16,17 will not be reviewed unless reported in the context of large clinical series or nonanecdotal reports. 18,19 …”

Section: Classificationmentioning

confidence: 99%

Clinical Operational Tolerance After Renal Transplantation

et al. 2010

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In solid organ transplantation, the achievement of an immunosuppression (IS)-free state [also referred to as clinical operational tolerance (COT)] represents the ultimate goal. Although COT is feasible and safe in selected cases after liver transplantation, it is an exceptional finding after other types of solid organ transplantation. In the field of renal transplantation (RT), approximately 100 cases of COT have been reported to date, mainly in patients who were not compliant with their immunosuppressive regimens or in individuals who had previously received a bone marrow transplant for hematological disorders. On the basis of promising results obtained in animal models, several tolerogenic protocols have been attempted in humans, but most have failed to achieve robust and stable COT after RT. Molecule-based regimens have been largely ineffective, whereas cell-based regimens have provided some encouraging results. In these latter regimens, apart from standard IS, patients usually receive perioperative infusion of donor bone marrow–derived stem cells, which are able to interact with the immune cells of the host and mitigate their response to engraftment. Unfortunately, most renal transplant patients who developed acute rejection—occurring either during the weaning protocol or after complete withdrawal of IS—eventually lost their grafts. Currently, the immune monitoring necessary for predicting the presence and persistence of donor-specific unresponsiveness is not available. Overall, the present review will provide a conceptual framework for COT and conclude that stable and robust COT after RT remains an elusive goal and that the different strategies attempted to date are not yet reproducibly safe or effective.

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“…In addition, cases of COT with follow-up shorter than 1 year 16,17 will not be reviewed unless reported in the context of large clinical series or nonanecdotal reports. 18,19 …”

Section: Classificationmentioning

confidence: 99%

Clinical Operational Tolerance After Renal Transplantation

et al. 2010

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“…Cases of COT following KTx as reported for the ideal situation of identical twins [8], or in whom the causes are unknown [9], are not further discussed here. Moreover, there are a number of published cases of COT with less than 1 year follow-up [10,11] or anecdotal reports [12,13], not further addressed here. Without doubt, most cases of COT following renal transplantation relate to patients who spontaneously stopped IS due to non-adherence to their immunosuppressive drugs.…”

Section: Progressmentioning

confidence: 99%

Tolerance in clinical transplantation: progress, challenge or just a dream?

Fändrich¹

2011

Langenbecks Arch Surg

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In combination with donor bone marrow-derived stem cells, some encouraging results in COT development were reported lately for renal transplantation as well. However, less toxic conditioning protocols and more experience by use of cell products with regulatory properties in combination with synergizing immunosuppressive drugs is required to launch future tolerance trials for a broader spectrum of potential transplant candidates. New methods in immunomonitoring including biomarkers, microarray-based genetic tolerance signatures and functional assays may pave the way to achieve COT in upcoming clinical trials.

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“…Previously, there have been many reports of ntES lines in mice, human and primates. Byrne et al (2007) produced primate ES cells by SCNT and there have been other attempts to produce human ES cells by SCNT (Cibelli et al, 2001;Heindryckx et al, 2007;Lavoir et al, 2005;Lu et al, 2003;Stojkovic et al, 2005 andTrivedi et al, 2006). Some of these attempts (Cibelli et al, 2001;Heindryckx et al, 2007 andLavoir et al, 2005) failed to produce blastocysts due to poor oocyte quality.…”

Section: Introductionmentioning

confidence: 99%

“…One report (Lu et al, 2003) failed to prove the genetic origin of the cloned blastocyst. Another report by Trivedi et al (2006), described successful production of human ES cells by SCNT using a cumulus cell from the same oocyte donor as the donor cell.…”

Section: Introductionmentioning

confidence: 99%

Production and Characterization of Putative ntES Cells from Handmade Cloned Goat Embryos Derived from Adult Fibroblast Donor Cells

Dutta

Malakar

Akshey

et al. 2011

Journal of Reproductive and Stem Cell Biotechnology

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In the field of nuclear transfer handmade cloning (HMC) technique has been a relatively recent addition. In the present investigation attempts were made to efficiently derive stem cell from hand made cloned (HMC) embryos in goat using adult fibroblast donor cell and to characterize the derived putative ntES cell for their stemness. Oocytes were collected from slaughterhouse ovaries and matured in maturation medium containing TCM199 (HEPES modified), 1 µg/ml FSH, 10 µg/ml LH, 1 µg/ml Estradiol-17β, 3% BSA and 5% FBS. The efficiency of the donor fibroblast cell for nuclear transfer was also assessed and an overall cleavage and morula formation rate of 62.44%±3.9 & 35.30%±3.86 was obtained respectively. Genetic relationship between the cloned embryos and donor cells was established by PCR amplification of highly polymorphic goat major histocompatibility complex (MHC) class II DRB gene. The PCR products were further subjected to SSCP for confirming the genetic relationship conclusively. Stem cell colonies were successfully derived from HMC embryos obtained from fibroblast donor cell. Primary colony formation rate was 61.66%±4.62 for fibroblast donor cell derived embryos. The putative ntES colonies were positively characterized for extracellular markers like alkaline phosphatase, TRA-1-60, TRA-1-81, SSEA-1, SSEA-4 by immunocytochemistry and intracellular markers like Oct4, Sox2 and Nanog with reverse-transcription-PCR. The differentiating ability of the derived cells was tested by embryoid body formation. Then the derived putative ntES cells were successfully cryopreserved for further investigation. The study has established an efficient protocol for putative ntES cell derivation from HMC embryos using adult fibroblast as a donor cell. It could be concluded that the present investigation has substantial significance as patient specific ntES cells have proven their therapeutic significance.

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Embryonic Stem Cell Derived and Adult Hematopoietic Stem Cell Transplantation for Tolerance Induction in a Renal Allograft Recipient:—A Case Report

Cited by 14 publications

References 14 publications

Clinical Operational Tolerance After Renal Transplantation

Clinical Operational Tolerance After Renal Transplantation

Tolerance in clinical transplantation: progress, challenge or just a dream?

Production and Characterization of Putative ntES Cells from Handmade Cloned Goat Embryos Derived from Adult Fibroblast Donor Cells

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