【参考資料】米国防総省CDMRPの採択プロジェクト概要とAxoGen社の参画記事
１ バカンティ教授のCDMRP採択プロジェクト
Stress-Altered Stem Cells WithDecellularized Allograft To Improve Rate of Nerve Regeneration
Principal Investigator: VACANTI, CHARLES A
Institution Receiving Award: BRIGHAM AND WOMEN'S HOSPITAL
Program: PRORP
Proposal Number: OR120208
Award Number: W81XWH-13-1-0298
Funding Mechanism: Idea Development Award
Partnering Awards:
Award Amount: $710,212.64
View Technical Abstract
PUBLIC ABSTRACT
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Background: There are over 700,000 peripheral nervous system (PNS) injuries every year. Peripheral nerves are all the nerves that are not part of the spinal cord and the brain. Unlike the spinal cord, which cannot currently be repaired, the PNS can regenerate, but the rate is quite slow and the functional recovery is often quite poor. Peripheral nerve injuries are often an important component of orthopedic injuries, such as blast injuries to the arms and legs that are suffered by wounded warriors in the military. This proposed research uses a new type of stem cell, called a stress-altered stem cell, which can be created from normal blood cells by exposing the cells to various types of stress. This stress turns the white blood cell back into a stem cell and these cells can be used in combination with a three-dimensional nerve scaffold to attempt to regrow peripheral nerves more quickly and regain better function after injury. Stress-Altered Stem Cells: There is a lot of talk and promise about how stem cells are going to revolutionize medicine. To date most people have thought that only embryonic stem cells and very few adult stem cells could be used to treat injury and disease. All the other cells in the body are thought to be committed cells, meaning that they can't change into different types of cells the way that stem cells can. Preliminary work has indicated that this might not be true. Stress alteration may be able to turn a committed cell into a stem cell by exposing the cells to physical changes, changes in oxygen concentration, and changes in pH. Embryonic stem cells, which are thought to have a lot of promise, have moral and ethical issues associated with them based upon certain religious beliefs. Other types of adult stem cells require genetic and chemical modifications to the cells, which add additional regulatory and safety burdens. Stress-altered stem cells can be created by taking white blood cells and exposing the blood cells to the stresses mentioned above, turning them into stem cells. These stress-altered stem cells will then be used to attempt to speed the rate of peripheral nerve repairs. Study Design: The rates and quality of nerve regeneration will be compared between repairs supplemented with stress-altered stem cells and other types of adult stem cells. We hypothesize that stress-altered stem cells combined with peripheral nerve tissue-based 3-D scaffolds will markedly accelerate the rate and quality of nerve regeneration when used to repair nerve injuries. A rat nerve injury model will be used to test the stress-altered stem cells with the scaffold, and the rate of nerve repair will be compared to other stem cells and the scaffold itself. A commercial partner, AxoGen, will process the rat nerves, using the same procedures used for a nerve scaffold already used in patients. Impact: The proposed study will take 18 months to complete. If successful, it is expected that AxoGen, the commercial partner, will license the technology and bring the technology to market. Depending on the regulatory pathway required by the FDA, this will take at least an additional 3 years and possibly longer. If this innovative work is successful the immediate impact would be on the 700,000 people suffering from peripheral nerve injuries. However, the stress-altered stem cells could possibly be used much more widely to treat other diseases and injuries suffered by millions of people. The overall benefit is an endless source of a person's own specific stem cells that do not need to be frozen or stored, simply stress-altered when needed. Military Benefit: Individuals in the military who have suffered combat wounds have a high likelihood of suffering peripheral nerve injury. Currently, doctors take nerves from healthy tissue to replace injured tissue. Unfortunately, for severely wounded warriors there is not always available healthy tissue. When this happens the current solution is to use a peripheral nerve scaffold that helps guide the nerve to regrow. Stem cells from the wounded warrior would be stress-altered and added to the scaffold. Soldiers receiving the stem cell-supplemented scaffold are expected to have faster and more robust recovery. This speedier and fuller recovery will also have important positive effects on both the emotional and physical aspects that impact the quality of life for those who have given so much for our country. |
２ POMAHAC, BOHDAN 教授のCDMRP採択プロジェクト
Branched Nerve Allografts to Improve Outcomes in FacialComposite Tissue Transplantation
Principal Investigator: POMAHAC, BOHDAN
Institution Receiving Award: BRIGHAM AND WOMEN'S HOSPITAL
Program: PRMRP
Proposal Number: PR130861
Award Number: W81XWH-14-1-0545
Funding Mechanism: Technology/Therapeutic Development Award
Partnering Awards:
Award Amount: $1,116,080.00
PUBLIC ABSTRACT
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The Problem: Each year, more than 1.4 million people suffer traumatic peripheral nerve injuries in the United States. The injuries can be caused by something as simple as cutting one's hand on a wineglass, or as violent as an IED (improvised explosive device) explosion to the leg or face. Depending on the level of severity of the nerve injury, patients can experience anything from a mild tingling sensation to chronic pain to complete lack of mobility or function. Conventional Treatment: Traditionally, when a nerve is injured and a portion of the tissue is missing, surgeons have had to harvest nerve tissue from the patient's body to perform a successful nerve repair. The method, known as an autograft, often requires a second surgery and can result in increased pain, a higher risk of complications, and a longer prescribed recovery time for the patient. A second newly developed method called an allograft is a human nerve from a deceased individual whose biologic material has been stripped out of the nerve graft so as to not cause an immune reaction when putting foreign tissue into someone's body. Allografts help bridge nerve gaps while maintaining the tissue's pliability and natural microarchitecture. Allografts do not require a second surgery like autograft repair and provide an off-the-shelf choice for surgeons. Composite Tissue Transplantation: One of the most exciting advancements in medicine has been the successful transplantation of arms, hands and faces, called Composite Tissue Transplantation (CTT). CTT requires that many different surgical teams work closely together other the course of hours to procure the face or arms from a brain-dead donor and transplant them into the recipient without letting the tissues be without blood flow and oxygen for more than a few hours. The nerves of the transplanted tissues must be attached to the nerve ends of the patient. Sometimes this is difficult because the branched nerves of the transplanted tissues do not match the size and geometry of the patient's nerve ends. The CTT surgeon must then create a cable-tied branched autograft by harvesting individual autografts from the patient and tying them together. In CTT, creating cable-tied branched nerves takes up much valuable time and reduces the chances for long-term success of the transplant. Proposed Product: This proposal is to help develop a medical product called a Branched Nerve Allograft that is intended to address complex nerve repair injuries. The Branched Nerve Allograft is a human nerve that has had the biologic material stripped out of the nerve and the remaining 3-D structure is used as an off-the-shelf replacement to suture the injured nerve ends together. Current products only include lengths of straight nerve that do not branch. This proposal is to create a new generation of product that would give a reconstructive surgeon the ability to repair more complex branched nerves by offering a product that connected to the end of the living nerve and whose branches could be sewn to multiple injured nerve stumps. Project Team: This product development effort is led by Dr. Bohdan Pomahac, the leading facial CTT surgeon in the country at the Brigham & Women's Hospital, along with Lieutenant Comander Ian Valerio, a reconstructive surgeon from Walter Reed National Military Medical Center in Bethesda, Maryland. AxoGen is the commercial partner for the project and currently produces the only commercially available processed nerve allograft that is straight, not branched. Impact: If this product development is successful, the branched nerve allograft will have been used in a facial transplant conducted on swine, which will provide both a proof of principle and evaluate effectiveness. It would lead to a medical product that surgeons could use in CTT to reduce surgical time and improve outcomes. In other complex nerve injuries, it would eliminate the need for autografts. Complex nerve injuries, especially branched nerves, currently do not have a satisfactory treatment until now. |
３ AxoGen社の両プロジェクト参画記事
AxoGen,Inc. Receives Department of Defense Funding for Next Generation PeripheralNerve Repair Research
$1.9 Million in Grant funding will exploreapplication of novel stem cells and development of branched grafts for complexnerve repair
Alachua, FL (PRWEB) June 04, 2014
AxoGen, Inc. (NASDAQ: AXGN), the emergingleader of the $1.6 billion U.S. peripheral nerve repair market, announced todaythat it would share in the award of two Department of Defense Grants totalingapproximately $1.9 million with Brigham and Women’s Hospital in Boston (BWH).
The grants, awarded to PrincipalInvestigators Charles Vacanti, MD and Bohdan Pomahac, MD, both of Brigham andWomen’s Hospital, will support development of next generation commercialsolutions to help the nearly 1 million people in the United States who undergosurgical repair for peripheral nerve injuries annually.
“I am excitedabout the potential to address challenging nerve repair cases through the useof regenerative medicine and stem cell therapies,” said Vacanti, who ischairman of Anesthesiology at BWH and Principal Investigator on the first grantof approximately $700,000. The grant will explore the promise of stem celltherapies in combination with Avance® Nerve Graft, a processed human nerveallograft currently marketed by AxoGen, to enhance nerve regeneration.
Pomahac, director of Plastic SurgeryTransplantation at BWH, will serve as Principal Investigator for the secondgrant of approximately $1.2 million to study the development of branchedperipheral nerve allografts to help improve the aesthetic and functionaloutcomes of complex facial injuries. “During complex reconstructions, manuallyrecreating branching nerve segments is both time consuming and technicallychallenging. This grant provides us the opportunity to develop a branched nerveallograft product for implantation,” said Pomahac.
“As a leader inthe surgical repair and regeneration of peripheral nerves, AxoGen is committedto the development of innovative products to serve the needs of surgeons andtheir patients,” commented AxoGen CEO Karen Zaderej. “The Department of Defenserecognizes the importance of innovation in this area and we are excited topartner with Brigham and Women’s Hospital to develop additional options forcomplex nerve reconstructions.”
The two grants will be funded through theCongressionally Directed Medical Research Program.
About AxoGen, Inc.
AxoGen (NASDAQ: AXGN) is a leading medicaltechnology company dedicated to peripheral nerve repair. AxoGen's portfolio ofregenerative medicine products is available in the United States, Canada andseveral European countries and includes Avance® Nerve Graft, the onlyoff-the-shelf commercially available processed nerve allograft for bridgingsevered nerves without the comorbidities associated with a second surgicalsite, AxoGuard® Nerve Connector, a porcine submucosa extracellular matrix("ECM") coaptation aid for tensionless repair of severed nerves, andAxoGuard® Nerve Protector, a porcine submucosa ECM product used to wrap andprotect injured peripheral nerves and reinforce the nerve reconstruction whilepreventing soft tissue attachments.
Avance® Nerve Graft is processed in theUnited States by AxoGen. AxoGuard® Nerve Connector and AxoGuard® NerveProtector are manufactured in the United States by Cook Biotech Incorporated,and are distributed exclusively by AxoGen. AxoGen maintains its corporateoffices in Alachua, Florida and is the parent of its wholly owned operatingsubsidiary, AxoGen Corporation
