21St Century Medicine Inc.

American National Red Cross

Other

Organ, Inc.

Life Resuscitation Technologies, Inc.

Organ Recovery Systems, Inc.

Lrt, Inc.

Intervene Biomedical

The United States of America as Represented by the American National Red

Intervene Immune Inc.

Gregory M Fahy

Bijan S Khirabadi

Yasumitsu Okouchi

Thomas Maciag

Brian Wowk

Michael G Federowicz

Lancer Brown

Lawrence E Wood

Robert T Brooke

Jun Wu

The present disclosure relates to an improved process of organ perfusion with vitrifiable concentrations of cryoprotective agents. In one implementation, the method may include perfusing an organ with a first solution containing a vitrifiable concentration of cryoprotectant at a temperature at or above −10° C. and perfusing the organ with a second solution containing a higher concentration of cryoprotectant than the first solution. The first solution may be adapted to vitrify at a cooling rate of less than 20° C./min, and the second solution may be adapted to vitrify at a cooling rate of less than 5° C./min. The perfusing with the second solution may begin at or above −10° C. and cause the organ to decline in temperature to below −10° C.

Methods for introduction and prolonged washout by organ perfusion of maximally vitrifiable cryoprotectant solutions at elevated temperatures

A combination of medications and medication doses is disclosed whereby age-related changes in systemic inflammation, cancer risk, heart disease risk, CD38 expression, hair color, thymotrophic hormones, immune cell populations, the CD4/CD8 cell ratio, bone marrow density, thymus structure, kidney function, and epigenetic age can be reversed in humans. Surprisingly, agents that accelerate the growth of cells reduce cancer risk, agents that intensify immune responses attenuate age-related inflammation, agents with no prior connection to hair color reverse age-related hair whitening, and a combination of agents that induces IGF-1, a hormone previously thought to drive systemic aging, results in a reversal of systemic aging as documented by an epigenetic clock. Medication combinations useful in the present invention include human growth hormone (GH) or GH releasers, dehydroepiandrosterone (DHEA), and metformin.

Pharmaceuticals and dosing means for human aging reversal

This invention relates to the preservation of vascularized tissues and organs by freezing or by vitrification; to organ and tissue cryopreservation or banking; and to tissue and organ perfusion with cryoprotective agents (also known as cryoprotectants).

Method of introduction and removal of high concentrations of cryoprotectants by vascular perfusion

The current invention involves administration to a cancer patient of a combination of therapeutic agents that, as a combination, has more efficacy against brain cancer than any currently available chemotherapeutic agent or chemotherapeutic combination, and that has essentially no toxic effects.

Effective, non-toxic treatments for brain cancer

A nutritional composition and method is provided in which telomerase expression can be safely activated in living cells. The nutritional composition can induce TERT mRNA or h-TERT mRNA and telomerase in vitro and in vivo while at the same time inhibiting potential side effects, helping to prevent certain types of cancer, and slowing the growth of any cancer cells that may exist in vivo. The method entails exposing cells to L-carnosine concentrations in the range of 51-100 mM or to a combination of L-carnosine and L-fucose in which the concentration of L-carnosine is 30-100 mM and the concentration of L-fucose is in the range from 0.1 micromolar to 100 mM.

Nutritional activation of telomerase in vitro and in vivo with increased safety

Methods and compositions are provided for the cryopreservation of human organs and tissues. In certain embodiments, Step 1 comprises perfusion with a vitrifiable cryoprotectant solution at a temperature above &#x2212;10&#xb0; C. for a time insufficient for the approximate osmotic equilibration of the organ with the solution, followed by cooling the organ to below &#x2212;10&#xb0; C. by perfusion with said solution at a reduced temperature. In certain embodiments, Step 2 comprises increasing the concentration of cryoprotectant further at a temperature from &#x2212;10 to &#x2212;40&#xb0; C. In certain embodiments, Step 3 comprises cooling and vitrifying the organ, rewarming it, and perfusing the organ with a vitrifiable concentration of cryoprotectant whose temperature is either raised gradually or is held at &#x2267;&#x2212;15&#xb0; C. Compositions are provided that allow safe organ perfusion with vitrifiable media at &#x3e;&#x2212;10&#xb0; C. and almost complete avoidance of chilling injury at &#x2212;20 to &#x2212;25&#xb0; C. and that allow slow warming after vitrification without freezing.

Methods and compositions for the cryopreservation of organs

Disclosed herein are aqueous carrier solutions for cryoprotectants that are useful for a variety of cryoprotectant solutions for use with cells, tissues, and whole organs, said aqueous carrier solutions permitting antinucleators to be fully effective in vitrification solutions, thereby allowing vitrification solutions to attain extreme effectiveness, and compatible vitrification solution compositions for use with these carrier solutions. The carrier solutions comprise lactose, mannitol or trehalose, and glucose in combination with other beneficial ingredients.

Advantageous vitrifiable cryoprotectant mixtures

Polyglycerol, lactose, and a combination of polyglycerol and lactose are effective at preserving cells, tissues, and organs from damage due to hypothermic, ischemic, or other metabolic impairment, and a mixture of polyglycerol plus lactose is particularly useful for the hypothermic storage of cells, tissues, and organs. The mixture of polyglycerol and lactose can be further improved by the addition of chondroitin sulfate, chlorpromazine, calcium, citrate, glutathione, adenine, glucose, magnesium, and a pH buffer.

Polyglycerol compositions for the protection of living systems from states of reduced metabolism

This invention relates generally to cryopreservation and a method for preventing injury caused by cooling and warming of tissue and for reducing the toxicity of vitrification solutions. The present method achieves reduction or elimination of injury by increasing the tonicity of the medium to greater than isotonic prior to cooling. The method was developed by attempting to simulate without freezing, the events that take place during freezing living cells and/or tissue. A further benefit of the method is that, since the cryopreservation medium is hypertonic, it can be diluted to a more extreme degree in one step once the system is rewarmed, without engendering the degree of cell swelling that would attend the same dilution factor when diluting an isotonic cryopreservation medium.

Hypertonic reduction of chilling injury

Human growth hormone therapy and thymic regeneration are effected by the generally simultaneous administration of one of human growth hormone, its analogs, precursors, metabolites, releasers or mixtures thereof in combination with one of DHEA, its precursors, releasers, analogs, metabolites or combinations thereof.

Method for the prevention of transplant rejection

Polyglycerol and lactose compositions for the protection of living systems from states of reduced metabolism

Disclosed herein is a carrier solution for cryoprotectants that is useful for use with cells, tissues, and whole organs and for a variety of cryoprotectant solutions and that permits antinucleators to be fully effective in vitrification solutions, thereby allowing vitrification solutions to attain extreme effectiveness, and compatible vitrification solution compositions for use with this carrier solution. The carrier solution comprises lactose and mannitol as well as other beneficial ingredients.

Advantageous carrier solution for vitrifiable concentrations of cryoprotectants, and compatible cryoprotectant mixtures

A dispersal pattern of hydrogen bonding sites on an ice surface is used as a template in a process for the design, selection and manufacture of synthetic ice interface dopants. Ice interface dopants are generally molecules which bind to a surface of an ice crystal and inhibit subsequent gain or loss of water molecules. The ice interface dopants can thus inhibit ice crystal growth, recrystallization, and sublimation. Ice interface dopants can also inhibit heterogeneous nucleating agents, and thus postpone or prevent ice nucleation. On the other hand, very strong IIDs may be used as well to beneficially induce ice nucleation. Exemplary dopant structures are provided that achieve near-perfect ice-bonding efficiency while being thoroughly adaptable to a wide variety of specialized ice-bonding applications. Orbital steering provides for steering lone pair orbitals of ice bonding atoms in the interface dopant to result in an optimal angular alignment with the complementary binding sites on ice.

Methods of using ice-controlling molecules

A cryoprotectant solution used for preserving biological material comprising cells is disclosed. The solution comprises dimethyl sulfoxide, an amide such as formamide, urea, acetamide, hydroxyurea, N-methyl formamide, and ethylene glycol or ethylene glycol in combination with propylene glycol wherein the propylene glycol replaces less than 8% w/v of the ethylene glycol.

Cryoprotectant solution containing dimethyl sulfoxide, an amide and ethylene glycol

A dispersal pattern of hydrogen bonding sites on an ice surface is used as a template in a process for the design, selection and manufacture of synthetic ice interface dopants. Ice interface dopants are molecules which when bound to a surface of an ice crystal inhibit the incorporation of additional water molecules into the crystal. The ice interface dopants thus inhibit ice crystal growth, recrystallization, and sublimation. Ice interface dopants can also inhibit heterogenous nucleating agents, and thus postpone or prevent ice nucleation. Exemplary dopant structures are provided that achieve near-perfect ice-bonding efficiency while being thoroughly adaptable to a wide variety of specialized ice-bonding applications. Orbital steering provides for steering lone pair orbitals of ice bonding atoms in the interface dopant to result in an optimal angular alignment with the complementary binding sites on ice.

Growing community of inventors

Gaithersburg, MD, United States of America

Gregory M Fahy