Adipose derived stem cell exosomes and uses thereof
Inventors
Cooper, Denise R. • Gould, Lisa • Patel, Niketa • WU, MACK
Assignees
University of South Florida • US Department of Veterans Affairs • Office of General Counsel of VA • University of South Florida St Petersburg
Publication Number
US-12016884-B2
Publication Date
2024-06-25
Expiration Date
2037-08-30
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Abstract
Provided herein are exosomal compositions and exsosomal lncRNA compositions and formulations thereof. Also provided herein are methods of treating a wound in a subject in need thereof that can contain the step of administering an exosomal composition and/or exsosomal lncRNA compositions or formulation thereof to a wound in a subject in need thereof.
Core Innovation
The invention provides pharmaceutical formulations containing an effective amount of exosomes derived from adipose stem cells, particularly from lean subjects, where the exosomes contain specific long non-coding RNAs (lncRNAs), including MALAT1, VLDLR, or GAS5. The lncRNAs are present within the exosomes and are characterized by their sequence similarity to SEQ ID NOs.: 1-3. These formulations can be delivered with a pharmaceutically acceptable carrier and may be administered by various routes, including topical application and direct injection to wounds.
The problem addressed by this invention is the unmet need for improved compositions and treatments for chronic and recalcitrant wounds, especially prevalent in older individuals and veterans suffering from diabetes, spinal cord injury, multiple traumatic injuries, or burns. Current stem cell therapies, such as those based on bone marrow, require invasive harvesting techniques and lack standardization in delivery methods. There is a need for non-bone marrow based wound healing techniques and compositions that effectively increase the rate of wound healing.
By utilizing exosomes secreted by adipose-derived stem cells and/or specific lncRNAs contained within these exosomes, such as MALAT1, linc-VLDLR, and GAS5, the invention introduces methods and compositions for treating wounds, particularly recalcitrant or ischemic wounds. The exosomal compositions can be formulated in various dosage forms and concentrations, most notably with higher concentrations of MALAT1 lncRNA, which demonstrates enhanced wound healing effects both in vitro and in vivo. The methods include administering these compositions directly to wounds, allowing for faster and more efficient healing than with previous techniques.
Claims Coverage
There are two independent claims, each covering a key inventive feature related to pharmaceutical formulations containing specific exosomal lncRNAs and their method of use for treating recalcitrant wounds.
Pharmaceutical formulation comprising adipose stem cell-derived exosomes containing specific lncRNAs
A pharmaceutical formulation comprises an effective amount of exosomes derived from adipose stem cells obtained from a lean subject. The exosomes include lncRNAs selected from MALAT1 lncRNA (with a concentration greater than VLDLR lncRNA or GAS5 lncRNA), and either VLDLR lncRNA or GAS5 lncRNA. The concentration of MALAT1 lncRNA is specified to be greater. The sequences of the lncRNAs are defined as follows: - MALAT1 lncRNA: about 95-100% identical to SEQ ID NO.: 1 or a fragment of at least 20 contiguous nucleotides at 95-100% identity to SEQ ID NO: 1; - VLDLR lncRNA: 90-100% identical to SEQ ID NO.: 2 or a fragment of at least 20 contiguous nucleotides at 95-100% identity to SEQ ID NO: 2; - GAS5 lncRNA: 90-100% identical to SEQ ID NO.: 3 or a fragment of at least 20 contiguous nucleotides at 95-100% identity to SEQ ID NO: 3. The formulation includes a pharmaceutically acceptable carrier and the effective amount of exosomes can range from 0.001 pg to 500 μg or more.
Method of treating recalcitrant wounds by administering exosomal lncRNA-containing formulations
A method is provided for treating recalcitrant wounds in human subjects by administering to the wound a pharmaceutical formulation comprising exosomes containing lncRNA, where the exosomes are derived from adipose stem cells obtained from a lean subject. The lncRNA comprises MALAT1 lncRNA and VLDLR lncRNA or MALAT1 lncRNA and GAS5 lncRNA, with the concentration of MALAT1 lncRNA being higher. The pharmaceutical formulation is administered either topically or through direct injection at the wound site, and the amount of MALAT1, VLDLR, or GAS5 lncRNA is an effective amount sufficient to increase the rate of recalcitrant wound healing compared to exosomes without the lncRNA. The method specifies administration one or more times and covers a range of recalcitrant wounds, including chronic wounds and wounds resulting from non-healing ulcers, spinal cord injury, multiple traumatic injuries, or burns.
The inventive features encompass both a detailed pharmaceutical formulation of exosomes containing defined lncRNAs for enhancing wound healing, and a method for using such a formulation to treat various types of recalcitrant wounds.
Stated Advantages
The exosomal compositions and formulations can provide faster and/or more efficient wound healing than current techniques.
The compositions offer a non-bone marrow based approach to wound healing, avoiding invasive and painful bone marrow harvesting methods.
Formulations containing exosomal lncRNAs such as MALAT1 can increase the rate of wound healing, including in recalcitrant and ischemic wounds.
The exosomes and lncRNA compositions can be readily formulated for human or veterinary use with flexible routes of administration such as topical application or direct wound injection.
Administration of these formulations can increase angiogenesis, cell proliferation, and tissue remodeling in treated wounds.
Documented Applications
Treating recalcitrant wounds in subjects, including chronic and ischemic wounds.
Treating wounds due to non-healing ulcers from spinal cord injury, multiple traumatic injuries, or burns.
Increasing the rate of wound healing via topical or direct injection of exosomal lncRNA-containing formulations.
Application to both human and veterinary subjects requiring enhanced wound healing.
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