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Methods, Compositions and Articles of Manufacture for Enhancing Survivability of Cells, Tissues, Organs, and Organisms

a technology of survivability and composition, applied in the field of cell biology and physiology, can solve the problems of inability to prolong the life of the organism, inability to depend on temperature for extended periods, and inability to maintain the survivability of the organism, so as to improve enhance the survivability of biological matter, and reduce the damage of biological matter

Inactive Publication Date: 2008-07-17
ROTH MARK B +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

These methods enable the protection and potential recovery of biological matter by inducing a reversible hypometabolic state, reducing damage and enhancing survivability under adverse conditions without the limitations of hypothermia, such as during injuries or diseases.

Problems solved by technology

This stasis is incomplete and cannot be relied upon for extended periods.
Unfortunately, the expression of this reflex is not the same in all people, and is believed to be a factor in only 10-20% percent of cold-water immersion cases.
However, dependence on temperature can be problematic, as apparatuses and agents for producing such low temperatures may not be readily available when needed or they may require replacement.
For example, tissue culture cells are often stored for periods of time in tanks that hold liquid nitrogen; however, these tanks frequently require that the liquid nitrogen in the unit be periodically replaced, otherwise it becomes depleted and the temperature is not maintained.
Furthermore, damage to cells and tissue occurs as a result of the freeze / thaw process.
Moreover, the lack of ability to control cellular and physiologic metabolism in whole organisms subjected to traumas such as amputation and hypothermia is a key shortcoming in the medical field.

Method used

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  • Methods, Compositions and Articles of Manufacture for Enhancing Survivability of Cells, Tissues, Organs, and Organisms
  • Methods, Compositions and Articles of Manufacture for Enhancing Survivability of Cells, Tissues, Organs, and Organisms
  • Methods, Compositions and Articles of Manufacture for Enhancing Survivability of Cells, Tissues, Organs, and Organisms

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preservation of Nematodes in Carbon Monoxide

[0675]The atmosphere contains 210,000 ppm oxygen. Exposure to low levels of oxygen, or hypoxia, results in cellular damage and death in humans. In the nematode, C. elegans, oxygen concentrations between 100 ppm and 1000 ppm are also lethal. By critically studying the response of nematodes to a range of oxygen tensions, it was found that oxygen concentrations below 10 ppm and above 5000 ppm are not lethal. In 10 ppm oxygen balanced with nitrogen, nematodes enter into a state of reversible suspended animation in which all aspects of animation observable under the light microscope ceases (Padilla et al., 2002). In oxygen concentrations of 5000 ppm (balanced with nitrogen) and above, nematodes progress through their life cycle normally. In a search for drugs that protect nematodes against hypoxic damage, carbon monoxide was tested.

[0676]To achieve specific atmospheric conditions the following apparatus was used: a glass syringe barrel having a...

example 2

Preservation of Human Skin in Carbon Monoxide

[0679]Carbon monoxide is extraordinarily toxic to humans because it strongly competes with oxygen for binding to hemoglobin, the primary molecule that distributes oxygen to tissues. The fact that nematodes, which do not have hemoglobin, are resistant to carbon monoxide and even protected against hypoxic damage by this drug suggested the possibility that carbon monoxide would protect against hypoxic damage in human tissue in situations where blood is not present, such as in tissue transplant or blood free surgical fields. To tested this hypothesis using human skin.

[0680]Three human foreskins were obtained for this purpose. The foreskin tissue was preserved in keratinocyte growth medium (KGM) containing insulin, EGF (0.1 ng / ml), hydrocortisone (0.5 mg / ml) and bovine pituitary extract (approx. 50 micrograms / ml of protein). Foreskins were rinsed in PBS, and excess fatty tissue was removed. Each foreskin sample was divided into 2 equal pieces....

example 3

Further Preservation Experiments with Nematodes

[0683]The following example contains information that overlaps and extends the information disclosed in Example 1.

A. Materials and Methods

[0684]Environmental chambers and apparati. Oxygen deprivation experiments were carried out using a custom atmospheric chamber designed by W. Van Voorhies (Van Voorhies et al., 2000). The chamber is a 30 mL glass syringe (Fisher #14-825-10B) fitted with a custom steel stopper that is lined with two viton O-rings to ensure a tight seal. The stopper is bored through and has a steel lure lock on the exterior face so that a hose carrying compressed gas can be attached. A defined gas mixture is delivered to the chamber at a constant pressure and flow rate from compressed tanks by passing first through a rotometer (Aalborg, flow-tube number 032-41ST) or mass flow controller (Sierra Instruments #810) to monitor flow rate and then through a 500 ml gas washing bottle (Fisher #K28220-5001) containing 250 ml wate...

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Abstract

The present invention concerns the use of oxygen antagonists and other active compounds for inducing stasis or pre-stasis in cells, tissues, and / or organs in vivo or in an organism overall, in addition to enhancing their survivability. It includes compositions, methods, articles of manufacture and apparatuses for enhancing survivability and for achieving stasis or pre-stasis in any of these biological materials, so as to preserve and / or protect them. In specific embodiments, there are also therapeutic methods and apparatuses for organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer using the active compounds described.

Description

[0001]This application is related to U.S. Provisional Patent Applications 60 / 673,037 and 60 / 673,295 both filed on Apr. 20, 2005, as well as U.S. Provisional Patent Application 60 / 713,073, filed Aug. 31, 2005, U.S. Provisional Patent Application 60 / 731,549, filed Oct. 28, 2005, and U.S. Provisional Patent Application 60 / 762,462, filed on Jan. 26, 2006, all of which are hereby incorporated by reference in their entirety.[0002]The government may own fights in the present invention pursuant to grant number GM048435 from the National Institute of General Medical Sciences (NIGMS).BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The present invention relates generally to the field of cell biology and physiology. More particularly, it concerns methods, compositions and apparatuses for enhancing survivability of and / or reducing damage to cells, tissues, organs, and organisms, particularly under adverse conditions, including but not limited to hypoxic or anoxic states, using on...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/66A61K31/555A61K31/185A61K31/165A61K31/275A61K31/26A61K31/095A61K31/21A61P43/00
CPCA01N1/02Y10S514/921A61K31/095A61K31/165A61K31/185A61K31/21A61K31/26A61K31/275A61K31/555A61K31/66A61K45/06A01N1/0226A61K33/04A61K2300/00A61P17/02A61P41/00A61P43/00A61P7/00A61P7/04A61P7/06A61P9/00A61P9/10
Inventor ROTH, MARK B.MORRISON, MIKEBLACKSTONE, ERICMILLER, DANA
Owner ROTH MARK B
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