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Compositions and methods for cell transplantation

Inactive Publication Date: 2013-11-14
UNIVERSITE CATHOLIQUE DE LOUVAIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a combination therapy to prevent the harmful effects of transplanting cells that can cause blood clots. The therapy involves giving the patient a combination of an antithrombin activator and a thrombin inhibitor. This combination is more effective and safe than using either treatment alone. The thrombin inhibitor used is bivalirudin, which has a short half-life, allowing for a quick return to normal blood clotting. This therapy is useful for reducing the risk of complications associated with cell therapy-induced blood clots.

Problems solved by technology

The procoagulant activity of stem and progenitor cells may be of concern for transplantation of these cells, in particular may cause undesired bloodstream modifications, loss of the transplanted cells, reduction of the cell engraftment potential and / or thrombotic events.
Moreover, this procoagulant activity cannot be controlled by unfractionated heparin, the conventional anticoagulant for hepatocyte transplantation.

Method used

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  • Compositions and methods for cell transplantation
  • Compositions and methods for cell transplantation
  • Compositions and methods for cell transplantation

Examples

Experimental program
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example 1

Materials and Methods

Cell Preparations

[0173]Adult-derived human liver mesenchymal stem cells (ALDSC, ADHLSC) were obtained from healthy liver donors as previously described (Najimi et al. Cell Transplant., 2007, vol. 16: 717-28). Cells were suspended in an albumin solution containing or not heparin at a concentration of 10 U / ml (or more when specified). As a control cryopreserved / thawed human hepatocytes were used. Liver isolation and hepatocyte cryopreservation / thawing procedures were previously published in detail (Sokal et al. Transplantation, 2003, vol. 76, 735-738). Human fibroblasts were collected by skin biopsy (medio-anterior side of the forearm) of 8 years old to 35 years old volunteers after written informed consent as previously described (Lysy et al. Hepatology, 2007, vol. 46, 1574-1585). Bone marrow samples were collected by aspiration of vertebrae or iliac crests of postmortem donors aged 8 to 67 years. Aspirates were collected into heparinized syringes containing 10% ...

example 2

Procoagulant Activity of Adult-Derived Human Liver Mesenchymal Stem Cells

[0181]Procoagulant activity of adult-derived human liver mesenchymal stem cells (ALDSC, ADHLSC) was demonstrated by a thromboelastometry method. This procoagulant activity is more important than that of the mature hepatocytes as evaluated by clotting time in the thromboelastograph test (FIG. 1). Furthermore, and conversely to hepatocyte procoagulant activity, it is shown that the ALDSC procoagulant activity is not fully inhibited by unfractionated heparin, low molecular weight heparin (data not shown), anti-vitamin K drugs (data not shown) or anti-thrombin drugs used alone (hirudin, bivalirudin) (FIGS. 2-3). We found that the concomitant use of unfractionated heparin and hirudin or bivalirudin is an original specific and synergistic combination allowing to modulate the pro-coagulant activity of adult-derived human liver mesenchymal stem cells (FIGS. 4-5). We also demonstrated a procoagulant activity of fibrobla...

example 3

Adult-Derived Human Liver Mesenchymal Stem Cells Express TF

[0182]The expression of TF and its natural inhibitor TFPI at the mRNA level using RT-PCR was assayed (FIG. 8). Both the membrane form and the alternatively-spliced variant of TF mRNA (as-TF) were expressed in adult-derived human liver mesenchymal stem cells (ALDSC). In additional experiments, real-time RT-PCR was used to quantify TF, as-TF, TFPI mRNA levels as shown in FIG. 9.

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Abstract

The present invention relates to compositions and methods for cell transplantation. In particular, the present invention provides a composition comprising procoagulant cells and at least one antithrombin activator, preferably unfractionated heparin, as well as at least one thrombin inhibitor, preferably bivalirudin.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the field of tissue regeneration in general and cell transplantation in particular. The present invention is directed at compositions and methods for improving cell transplantation and particularly for inhibiting procoagulant activity associated with cell transplantation.BACKGROUND OF THE INVENTION[0002]Various conditions caused by diseased or otherwise damaged or functionally impaired organs may be treated by organ transplantations. In particular, transplantation of heart, kidneys, liver, lungs, pancreas, intestine, and thymus can routinely be performed with a reasonable rate of success. A major drawback in organ transplantation however remains the need to find a compatible donor for each recipient patient, since incompatibility between the donor and recipient may result in rejection of the transplanted organ. Transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match an...

Claims

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Application Information

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IPC IPC(8): A61K35/28A61K31/737A61K38/58A61K31/727A61K38/55A61K35/407
CPCA61K35/28A61K31/727A61K38/55A61K38/58A61K31/737A61K35/407A61K45/06A61K31/5377A61P1/16A61P7/02A61P9/10A61K2300/00
Inventor STEPHENNE, XAVIERSOKAL, ETIENNENAJIMI, MUSTAPHAEECKHOUDT, STEPHANEHERMANS, CEDRIC
Owner UNIVERSITE CATHOLIQUE DE LOUVAIN
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