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Compositions and methods for tissue preservation at ambient or subnormothermic temperatures

A composition and biological tissue technology, applied in the preservation of human or animal bodies, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of tissue and cell damage, injury, etc.

Inactive Publication Date: 2018-08-03
PRESIDENT & FELLOWS OF HARVARD COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, storage at such a low temperature inevitably caused tissue and cell damage, and nearly 6 hours of storage made the damage irreversible

Method used

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  • Compositions and methods for tissue preservation at ambient or subnormothermic temperatures
  • Compositions and methods for tissue preservation at ambient or subnormothermic temperatures
  • Compositions and methods for tissue preservation at ambient or subnormothermic temperatures

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0153] In the examples below, the tables are indicated with Arabic numerals (e.g. Table 1, Table 2, Table 3, etc.).

[0154] Over the past 40 years, remarkable progress has been made in the preservation of solid organs such as livers, kidneys, and preservation in vitro for up to hours. Unfortunately, this same approach cannot be applied to heart storage, which can only be stored in vitro for 4-6 hours even after decades of painstaking efforts (Churchill TA. Organ preservation for transplantation. In: Storey KB, editor. Functional Metabolism: regulation and adaptation. John Wiley-Liss; 2004; 529-55). Major advances have included the conceptual development of preservation solutions such as Celsior and the University of Wisconsin solution (UWS; Table 1-1), which were formulated based on the prevention of edema during "cold storage at 4°C"—a method used in organ preservation. The ingrained notion that only short-term ex vivo storage of organs is permitted. The existence of this ...

Embodiment 2

[0186] This case examines whether the recovery of cardiac function after storage is proportional to the maintenance of the energy state of the organ and the storage temperature, and compares cardiac preservation at 4°C, 13°C, and 21°C in Celsior and Somah solutions, respectively.

[0187] Materials and methods

[0188] Heart extraction surgery, in vitro heart storage, ATP and phosphocreatine assays, preparation of hearts for ex vivo resuscitation and functional studies, preparation of blood for ex vivo studies, Somah device and functional studies were performed as described in Case 1 ,above.

[0189] Heart weighing and biopsy. The heart chambers were emptied for weighing before the start of storage and after 5 hours. Cardiac punch biopsies (2–4 mm in diameter) were removed using punch forceps for histopathology (HP; hematoxylin and Eosin staining) and ultrastructure of Somah hearts and HEP determination of Somah and Celsior hearts.

[0190] Electron microscopy of Somah hea...

Embodiment 3

[0225] In this example, a heart harvested 30 minutes after cyclic cardiac death (DCD heart) was studied, and its storage was equivalent to 4-5 times the current clinical standard. Furthermore, the study aimed to determine the ideal temperature for long-term storage of DCD hearts in Somah in a functionally viable state for transplantation.

[0226] Materials and methods

[0227] Animal Model Three-month-old male Sprague-Dawley rats were used in strict accordance with the protocols approved by the Animal Research Subcommittee.

[0228] Solution preparation and other materials. Somah's solution was prepared as described above. Freshly prepared solutions were filter sterilized at 4° C. using a 0.4 mm filter (Vidaur) and used within 24 hours. Unless otherwise stated, all chemical reagents and antibodies were obtained from Sigma Chemicals, Inc. (St. Hercules, CA) or Danco Corporation (Carpinteria, CA, USA).

[0229] Cardiac Extraction, Storage, and Simulated Reperfusion Rats we...

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Abstract

Provided herein are methods and compositions for resuscitating, storing, and preserving the functional integrity of organs and tissues at ambient temperatures for up to 24 hours. Metabolic function ismaintained by sustaining ATP levels, mitochondrial function, prevention of edema, and by regulating calcium, sodium, potassium, magnesium, and chloride ions.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 173,184, filed June 9, 2015, which is hereby incorporated by reference in its entirety. [0003] Government interests [0004] The invention was made with the support of the government, and won the Excellence Award issued by the U.S. Department of Veterans Affairs, No. BX000817-01A1. The government has certain rights to this invention. technical field [0005] The present invention mainly relates to compositions and methods for preserving biological tissues and organs at ambient temperature for a long time. Background technique [0006] The main obstacles to organ transplantation are the limited availability of donor organs and their poor quality, which is attributed to degradation during storage. This is especially evident in heart donors, where the limit of in vitro storage time is 4-6 hours. The currently used extracorporeal heart preservatio...

Claims

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Application Information

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IPC IPC(8): A01N1/00A01N1/02
CPCA01N1/0226A61K31/198A61K31/715A61K33/06A61K38/28A01N1/0247A01N1/0278
Inventor H·塔特
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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