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Methods for accelerating wound healing by administration of adipokines

a technology of adipokines and wound healing, applied in the direction of drug compositions, dermatological disorders, peptide/protein ingredients, etc., can solve the problems of impaired wound healing, inability to properly function, and inability to properly treat diabetic patients, so as to accelerate the effect of accelerating the healing process of damaged skin or skin wound

Inactive Publication Date: 2008-07-03
BRAIMAN WIKSMAN LIORA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides new methods for promoting the healing of damaged skin or skin wounds by administering adipokines, adipocyte modulators, or preadipocyte modulators to the skin cells colonizing the damaged area. This can be done by implanting adipocytes, preadipocytes, or stem cells into the damaged area or by administering a therapeutically effective amount of adipokines or viral vectors containing adipokine coding. The invention also covers a range of wound types, including ulcers, diabetic wounds, burns, and more. Overall, the invention provides new tools for treating skin damage and promoting healing."

Problems solved by technology

Wound healing is impaired when these components, either individually or as a whole, do not function properly.
Yet skin ulceration in diabetic patients takes a staggering personal and financial cost (Knighton and Flegel, 1993; Shaw and Boulton, 1997).
However, other mechanisms whereby the diabetic state associated with abnormal insulin signaling impairs wound healing and alters the physiology of skin has not been elucidated.
Another issue associated with impaired wound healing relates to infections of post surgical wounds occurring in 25% of patients hospitalized in surgical wards.
However, there is no teaching in the prior art for utilizing adipocytes, adipocyte or preadipocyte modulators, or molecules secreted by adipocytes, for inducing or accelerating the processes associated with wound healing.

Method used

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  • Methods for accelerating wound healing by administration of adipokines
  • Methods for accelerating wound healing by administration of adipokines
  • Methods for accelerating wound healing by administration of adipokines

Examples

Experimental program
Comparison scheme
Effect test

example 1

Association of Adipocytes with Migrating Keratinocytes During the Wound Healing Process

[0134]Migrating epidermal cells (keratinocytes) with recruited adipocytes were observed in 7-day-old wound tissue (FIG. 2). As can be seen in FIG. 1, migrating keratinocytes were observed across the wound gap in about 60% of the untreated wounds, and recruited adipocytes were also present in about 60% of the untreated wounds. FIG. 1 also shows that migrating keratinocytes and recruited adipocytes were observed in about 90% and 80% of insulin-treated wounds, respectively.

[0135]These results reveal that migration of keratinocytes to the wound gap area is closely associated with recruitment of adipocytes during an early stage of the wound healing process. The results thus indicate that migration of adipocytes to the wound area is involved in the wound healing process.

example 2

The Effect of PPARγ Modulators on Keratinocytes Migration and Wound Contraction

[0136]The effect of inhibiting or enhancing the activity of peroxisome proliferators-activated receptor gamma (PPARγ) on keratinocytes migration was evaluated utilizing the in vitro migration assay. Thus, primary keratinocytes were isolated and plated on 5 ml non-coated dishes until confluence in low Ca2+ medium, and an artificial crossover scratch was formed in each dish with a 200 μm tip. Cells were either non-treated (control) or treated daily with PPARγ modulators. As can be seen in FIG. 3, the treatment of cultured primary murine keratinocytes with the PPARγ antagonist GW9662 promoted keratinocytes migration. On the other hand, the treatment of cultured keratinocytes with the PPARγ agonist troglitazone inhibited keratinocytes migration (FIG. 8).

[0137]The effect of inhibiting or enhancing the activity of PPARγ using PPARγ antagonist and agonist, respectively, on wound healing was also evaluated in viv...

example 3

The Effect of Adipsin on Keratinocytes Migration and Wound Contraction

[0139]The effect of adipsin (complementing Factor D, which is secreted from adipocytes) on wound healing was evaluated in vivo. Accordingly, full thickness incision wounds were effected on the back of C57BL mice and were treated daily, for 6 days, with PBS buffer (control), or with 1 μM adipsin. The mice were sacrificed 6 days after wounding and the wounds were then analyzed. As illustrated in FIGS. 4-5 and 7, adipsin substantially promoted wound contraction. In addition, adipsin increased epidermal closure from about 15% to about 30%, and increased keratinocytes migration from about 30% to about 65%, as compared with the buffer control (FIG. 6).

[0140]These results demonstrate that an adipokine, such as adipsin, can effectively induce or accelerate wound healing.

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Abstract

Methods for inducing or accelerating a healing process of a damaged skin or skin wounds are described. The methods include administering to the skin cells colonizing the damaged skin or skin wound a therapeutically effective amount of an adipokine, an adipocyte or preadipocyte modulator, adipocytes, preadipocytes, or stem cells, or transforming the skin cells colonizing the damaged skin or skin wound such as to express and secrete an adipokine, thereby inducing or accelerating the healing process of the damaged skin or skin wound.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. Ser. No. 11 / 384,527 filed Feb. 7, 2006, which is a continuation-in-part application of PCT application No. PCT / IL2004 / 000727, filed Aug. 5, 2004, in which the US is designated, and claims the benefit of U.S. Provisional Patent Application No. 60 / 493,000, filed Aug. 7, 2003, now expired, the entire contents of each of and both these applications being hereby incorporated by reference herein in their entirety as if fully disclosed herein.FIELD AND BACKGROUND OF THE INVENTION[0002]The present invention relates to methods and pharmaceutical compositions for inducing and / or accelerating cell proliferation and / or cell migration and / or cell differentiation and thereby accelerating the healing process of wounds. More particularly, the present invention relates to the use of bioactive molecules which are secreted by adipocytes (adipokines), and bioactive molecules which modulate adipocytes and preadipocytes...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/19A61P17/02A61K
CPCA61K31/22A61K38/4826A61K38/22A61K35/35A61K35/28A61P17/02A61P43/00
Inventor BRAIMAN-WIKSMAN, LIORASOLOMONIK, INESSA
Owner BRAIMAN WIKSMAN LIORA
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