Cardiac Allograft Acceptance after Localized Bone Marrow Transplantation by Isolated Limb Perfusion in Nonmyeloablated Recipients

Askenasy, Nadir; Yoleuk, Esma S.; Shirwan, Haval; Wang, Zhiliang; Farkas, Daniel L.

doi:10.1634/stemcells.21-2-200

Cited by 9 publications

(5 citation statements)

References 45 publications

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“…3D). These phenotypic dynamics characteristic of donor hematopoietic progenitor activation upon homing to the host BM [30] showed a general trend of TNF receptor upregulation, with cells defined as lin À SCA-1 þ c-kit þ ubiquitously expressing the receptors throughout the early engraftment period.…”

Section: Characterization Of Tnf Receptor Expressionmentioning

confidence: 99%

Tumor Necrosis Factor Receptors Support Murine Hematopoietic Progenitor Function in the Early Stages of Engraftment

Pearl‐Yafe¹,

Mizrahi

Stein³

et al. 2010

Stem Cells

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Tumor necrosis factor (TNF) family receptors/ligands are important participants in hematopoietic homeostasis, in particular as essential negative expansion regulators of differentiated clones. As a prominent injury cytokine, TNF-a has been traditionally considered to suppress donor hematopoietic stem and progenitor cell function after transplantation. We monitored the involvement of TNF receptors (TNF-R) 1 and 2 in murine hematopoietic cell engraftment and their inter-relationship with Fas. Transplantation of lineage-negative (lin 2 ) bone marrow cells (BMC) from TNF receptor-deficient mice into wild-type recipients showed defective early engraftment and loss of durable hematopoietic contribution upon recovery of host hematopoiesis. Consistently, cells deficient in TNF receptors had reduced competitive capacity as compared to wild-type progenitors. The TNF receptors were acutely upregulated in bone marrow (BM)-homed donor cells (wild-type) early after transplantation, being expressed in 60%-75% of the donor cells after 6 days. Both TNF receptors were detected in fast cycling, early differentiating progenitors, and were ubiquitously expressed in the most primitive progenitors with long-term reconstituting potential (lin 2 ckit). BM-homed donor cells were insensitive to apoptosis induced by TNF-a and Fasligand and their combination, despite reciprocal inductive cross talk between the TNF and Fas receptors. The engraftment supporting effect of TNF-a is attributed to stimulation of progenitors through TNF-R1, which involves activation of the caspase cascade. This stimulatory effect was not observed for TNF-R2, and this receptor did not assume redundant stimulatory function in TNFR1-deficient cells. It is concluded that TNF-a plays a tropic role early after transplantation, which is essential to successful progenitor engraftment.

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Section: Characterization Of Tnf Receptor Expressionmentioning

confidence: 99%

Tumor Necrosis Factor Receptors Support Murine Hematopoietic Progenitor Function in the Early Stages of Engraftment

Pearl‐Yafe¹,

Mizrahi

Stein³

et al. 2010

Stem Cells

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“…Heterotopic heart transplantation was performed using a modified procedure for the mouse as described previously. 30,31 …”

Section: Construction Of Sa-fasl Chimeric Gene and Expression In Drosmentioning

confidence: 99%

Display of Fas Ligand Protein on Cardiac Vasculature as a Novel Means of Regulating Allograft Rejection

et al. 2003

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Background-Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts. Methods and Results-SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival timeϭ17.4Ϯ5 versus 9.6Ϯ1 days). Allograft survival was further extended to 21Ϯ2.6 and 24Ϯ3 days (PϽ0.05) by intravenous treatment of graft recipients with 1 dose of SA-FasL-decorated donor splenocytes on days 2 and 6 after transplantation, respectively. Conclusions-This study shows for the first time that exogenous proteins can be displayed on the endothelium of solid organs for therapeutic purposes. This approach provides a convenient and rapid means of displaying exogenous proteins on the surface of cells, tissues, and solid organs, with broad research and therapeutic implications.

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“…We have published extensively on this [131][132][133][134][135][136][137][138][139][140][141][142][143][144], with [139] a brief review of the most interesting findings. We could show that the HSCs were alive and functional after three weeks, having undergone a cycle of homing, adhesion, cluster formation, colonization, engraftment (and subsequent differentiation), just as predicted and hoped for, but with more details and mechanistic clues.…”

Section: Imaging Stem Cells In Vivomentioning

confidence: 99%

Biomedical Applications of Translational Optical Imaging: From Molecules to Humans

Farkas

2021

Molecules

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Light is a powerful investigational tool in biomedicine, at all levels of structural organization. Its multitude of features (intensity, wavelength, polarization, interference, coherence, timing, non-linear absorption, and even interactions with itself) able to create contrast, and thus images that detail the makeup and functioning of the living state can and should be combined for maximum effect, especially if one seeks simultaneously high spatiotemporal resolution and discrimination ability within a living organism. The resulting high relevance should be directed towards a better understanding, detection of abnormalities, and ultimately cogent, precise, and effective intervention. The new optical methods and their combinations needed to address modern surgery in the operating room of the future, and major diseases such as cancer and neurodegeneration are reviewed here, with emphasis on our own work and highlighting selected applications focusing on quantitation, early detection, treatment assessment, and clinical relevance, and more generally matching the quality of the optical detection approach to the complexity of the disease. This should provide guidance for future advanced theranostics, emphasizing a tighter coupling—spatially and temporally—between detection, diagnosis, and treatment, in the hope that technologic sophistication such as that of a Mars rover can be translationally deployed in the clinic, for saving and improving lives.

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Cardiac Allograft Acceptance after Localized Bone Marrow Transplantation by Isolated Limb Perfusion in Nonmyeloablated Recipients

Abstract: ). These data indicate that IL perfusion is a reliable alternative procedure for establishment of hematopoietic chimerism and donor-specific tolerance without myeloablative conditioning.

Cited by 9 publications

References 45 publications

Tumor Necrosis Factor Receptors Support Murine Hematopoietic Progenitor Function in the Early Stages of Engraftment

Tumor Necrosis Factor Receptors Support Murine Hematopoietic Progenitor Function in the Early Stages of Engraftment

Display of Fas Ligand Protein on Cardiac Vasculature as a Novel Means of Regulating Allograft Rejection

Biomedical Applications of Translational Optical Imaging: From Molecules to Humans

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