Treatment methods utilizing stem cell mobilizers and immunosuppressive agents

a technology of stem cell mobilization and immunosuppressive agent, which is applied in the field of organ transplantation, can solve the problems of affecting the quality of isle and survival rate, and achieve the effect of promoting allograft survival and provoking long-term allograft acceptan

Active Publication Date: 2018-06-14
WILLIAMS G MELVILLE +1
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach enhances allograft survival, induces long-term acceptance, and minimizes immunosuppression-related complications, allowing for improved patient outcomes and reduced side effects.

Problems solved by technology

Calcineurin inhibitors remain the mainstay of immunosuppression in organ transplantation, but are associated with important side effects such as infections, diabetes, hypertension, nephrotoxicity and malignancy which can influence quality of isle and survival rates.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Treatment methods utilizing stem cell mobilizers and immunosuppressive agents
  • Treatment methods utilizing stem cell mobilizers and immunosuppressive agents
  • Treatment methods utilizing stem cell mobilizers and immunosuppressive agents

Examples

Experimental program
Comparison scheme
Effect test

example 1

Induction of Liver Allograft Acceptance by Mobilizing Bone Marrow Stem Cells

Materials and Methods

[0097]Rat Strains and Care. DA (RTIAa) rats were purchased from Harlan ague-Dawley (Indianapolis, Ind.) and used at 8-12 weeks of age. The green fluorescent protein (GFP) transgenic Lewis (RTI1) rat strain was obtained from the National Institutes of Health (NIH)-funded Rat Resource and Research Center (RRRC), University of Missouri, Columbia, Mo. Animals were maintained in the specific pathogen-free facility of Johns Hopkins Medical Institutions. Animals were cared for according to NIH guidelines and under a protocol approved by the Johns Hopkins University Animal Care Committee.

[0098]Liver Transplantation. Orthotopic liver transplantation (OLT) was performed under isoflurane (Abbott laboratories, North Chicago, Ill.) inhalation anesthesia according to a method modified from previously described. Small liver transplantation consisted of removal of the left lateral lobe, tire left portio...

example 2

Induction of Kidney Allograft Acceptance by Mobilizing Bone Marrow Stem Cells

Materials and Methods

[0119]Rat Strains and Care. DA (RTIAa) rats were purchased from Harlan ague-Dawley (Indianapolis, Ind.) and used at 8-12 weeks of age. The green fluorescent protein (GFP) transgenic Lewis (RTI1) rat strain was obtained from the National Institutes of Health (NIH)-Funded Rat Resource and Research Center (RRRC), University of Missouri, Columbia, Mo. Animals were maintained in the specific pathogen-free facility of Johns Hopkins Medical Institutions. Animals were cared for according to NIH guidelines and under a protocol approved by the Johns Hopkins University Animal Care Committee.

[0120]Orthotopic Kidney Transplantation. An orthotopic kidney transplantation in rats was performed under isoflurane (Abbott Laboratories, North Chicago, Ill.) inhalation anesthesia according to the technique described by Dandier (1968). Specifically, the DA to Lewis model of acute rejection was studied. Briefl...

example 3

Induction of Skin Allograft Acceptance by Low Dose Immunosuppression and Mobilizing Bone Marrow Stem Cells

[0129]Allogenic skin has had a major role in acute burn care for over 100 years, and is the gold standard for temporary skin substitutes. The major obstacle to prolonged use is its immunogenicity.

[0130]Based on the data described herein, it is further hypothesized that mobilization of recipient bone marrow stem cells will facilitate a repopulation of skin allografts with recipient-derived cells and reduce or eliminate the need for immunosuppression in this population of patients where infection plays a major role in mortality. To test this hypothesis, skin transplants were performed from DA rats to Lewis rats, and recipient rats were treated with stem cell mobilizer (mozobil: AMD3100) and / or low dose immunosuppressant (Tacrolimus, FK-506).

Materials and Methods

[0131]Rat Strains and Care. DA (RTIAa) rats and C57 / B6 mice were purchased from Harlan ague-Dawley (Indianapolis, Ind.) a...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to the field of organ transplantation. In one aspect, the present invention provides methods of treating an organ transplant recipient comprising administering to the recipient a therapeutically effective amount of a stem cell mobilizer and an immunosuppressive agent. In particular embodiments, the present invention provides a method of treating an organ transplant recipient comprising administering to the recipient a therapeutically effective amount of an agent that mobilizes CD34+ and / or CD133+ stem cells and a low dose of an immunosuppressive agent.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 316,180, filed Mar. 22, 2010, and U.S. Provisional Application No. 61 / 285,602, filed Dec. 11, 2009, both of which are incorporated herein by reference in their entireties.STATEMENT OF GOVERNMENTAL INTEREST[0002]This invention was made with U.S. government support under grant no. AI065488. The U.S. government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates to the field of organ transplantation.BACKGROUND OF THE INVENTION[0004]As the early outcomes of human organ transplantation have dramatically improved, research focus has shifted toward solving the remaining problems associated with chronic immunosuppression. Calcineurin inhibitors remain the mainstay of immunosuppression in organ transplantation, but are associated with important side effects such as infections, diabetes, hypertension, nephrotoxicity and malignancy wh...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/436A61K45/06A61K38/13A61K38/19
CPCA61K31/436A61K38/193A61K38/13A61K45/06A61K31/00A61K31/365A61K31/395A61K31/4427A61K31/506A61K38/18A61K38/19A61P1/16A61P9/10A61P13/12A61P17/00A61P37/06A61K9/0019A61K9/08A61K9/10A61K9/107A61K9/2004A61K9/4841A61K9/0095A61K2300/00
InventorSUN, ZHAOLIWILLIAMS, GEORGE MELVILLE
OwnerWILLIAMS G MELVILLE