Rostock tissue bank collaborates with a leading company in regenerative medicine

Tissue Regenix Group plc is a leading international company in the development of regenerative implants based on cell-free tissue. This is the first time that Tissue Regenix is making its licenses available to a European tissue bank.

“This collaboration is a European milestone”, emphasised Tissue Regenix CEO, Antony Odell. “The prompt provision of high-quality tissue transplants is one aspect. The other aspect is that we wish to conduct research into new transplants together with our partners in Rostock and elsewhere in order to allow significantly better long-term outcomes for patients/recipients through increased quality and significantly reduced or no rejection reactions.”

Even eight years after the legal framework came into effect, care for patients with high-quality tissue transplants is unsatisfactory. Waiting times for eye corneas are approx. three months, with similar periods for cardiovascular tissues, that is, heart valves and vessels. Tissue transplants still have to be imported from abroad. In an emergency, a lack of suitable donor tissue can also have fatal consequences or lead to the permanent degradation of quality of life (e.g. amputation of limbs).

The law on the donation, extraction and transfer of organs and tissue (Transplantation Act) was amended and a special Tissue Act passed as far back as July 2007. The Tissue Act regulates the handling of human tissue and cells, as well as of medical grafts produced from human tissue. Nevertheless, the possible application of innovative technologies in the extraction and processing of tissue is still largely in its infancy. This groundbreaking German-British collaboration hopes to change this.

The foundation for this was laid last year with the founding of the non-profit Gewebebank Mecklenburg-Vorpommern (GBM-V) tissue bank and the non-profit Gesellschaft für Transplantationsmedizin Mecklenburg- Vorpommern (GTM-V gGmbH) in Rostock. GBM-V, the first multi-tissue bank of its type in Germany, is based at the Biomedical Research Centre (BMFZ) in Rostock and is a member of BioCon Valley e.V.

The initiators of this new path in tissue medicine in Mecklenburg-Vorpommern are Rostock doctors Dr. Frank-Peter Nitschke (55) and Dr. Axel Manecke (46), both of whom have years of experience in transplantation medicine. Both companies pursue exclusively non-profit purposes in the field of tissue medicine.

Goal 1: To inform and improve demand on donor tissues

GTM-V, which is cooperating with Gewebebank Mecklenburg-Vorpommern in Rostock, is one of the few facilities in Germany that provides for the entire spectrum of postmortem donations (extraction of eye corneas, bones, tendons, skin, heart valves, blood vessels after death) and some live donations (heart valves). “In future we will also provide complete coverage of live donations,” announced Nitschke. This encompasses donations from the placenta (amnion – caul from the amniotic sac), as well as muscular ans skeletal tissue. “The extraction of postmortem donations is essentially performed by our own medical specialists and in close cooperation with hospitals.”

Last year eleven hospitals in Mecklenburg-Vorpommern entered into an agreement with the Gesellschaft für Transplantationsmedizin Mecklenburg- Vorpommern (GTM-V). Three of these clinics are new in the network. The GTM-V donor programme started in July 2015. The number of donations or tissue extracted is constantly on the rise. “Here, we place great value on comprehensive information on tissue donations and transparency when dealing with human grafts,” emphasises Dr. Frank-Peter Nitschke.

Tissues extracted are currently still prepared for grafting in cooperating tissue banks. As far as the production of corneas is concerned, transplantation capacity is currently at 78 percent. A new procedure should increase transplantability to 95 percent. With cardiovascular and musculoskeletal tissues, this is already 100 percent. “It is, essentially, possible to cover the demand for tissue donations,” say transplantation specialists, convinced.

“New production technologies mean that the number of transplants, especially of corneas, heart valves, blood vessels and skin, is on the rise. We assume that the current number of approx. 8,000 cornea transplants will rise to approx. 12,000 in future, with approx. 1,000 heart and blood-vessel transplants nationwide every year. The demand for skin transplants is enormous, particularly for chronic wounds, burns, accidents and cancer operations.”

Goal 2: Innovative technologies to avoid rejection reactions

The collaboration with Tissue Regenix is primarily intended to secure access to regenerative grafts based on cell-free tissue scaffolds for affected patients. “The core aspect is Tissue Regenix's patented dCELL® technology,” explains Antony Odell. “Tissue Regenix collaborates internationally with leading research institutions in this field, for example with the University of Leeds, one of the most widely-recognised research institutions worldwide in the field of biomedicine. The company is based in Yorkshire, with a subsidiary in San Antonio, Texas, USA (Tissue Regenix Woundcare, Inc.). Tissue Regenix's current focus is on wound care, orthopaedics and cardiac and general surgery.”

The dCELL® technology removes hereditary information (DNA) and cellular remnants from the donor tissue and leaves a cell-free scaffold, attracting patient's own cells to seed and regenerate so that the new tissue is not recognised as foreign by the patient's body and is therefore not rejected.

The beginning of dCELL® research and technology was the decellularisation of human heart valves. The current available options for heart valves replacement are not satisfactory. In particular young patients, will need to take either take lifelong anticoagulants or have to compromise on durability for the grafted elements, what means in the consequence an increased risk of reoperations. Older patients, having a longer life expectancy, benefit too through longer durability of the grafts due to this technology.

dCELL® heart valves have now been implanted for ten years. More than 1,500 patients have so far been treated successfully with these grafts. The most recent publications in the European Journal of Cardio-Thoracic Surgery, one of the most well-known periodicals in heart surgery, document the success of this innovative technology (DOI: 10.1093/ejcts/ezu013, DOI: 10.16/jathoracsur.2010.08.022). Patients with a fresh dCELL® pulmonary human valve have so far not required any valve-related reoperation.

A further application is 'DermaPure', dCELL® skin recently introduced in the USA by Tissue Regenix. DermaPure was originally used in the treatment of diabetic wounds in particular, but has also proved highly effective in the treatment of other chronic wounds. In the field of orthopaedics, the focus is on partial replacement of the meniscus and injuries to the anterior cruciate ligament. The first clinical studies are now being performed in Europe, based on porcine dCELL@ tissue (originating from pigs).

“The further development of innovative grafts is an important part of our work,” emphasises Dr. Frank-Peter Nitsche. One partner is, for example, the Leibniz-Institut für Plasmaforschung und Technologie e.V. Greifswald (INP). Physical plasma is to be used to reduce and/or completely eliminate the bacterial contamination of tissue in order to prevent the transmission of infections. Furthermore, apart from the collaboration with Tissue Regenix, research into increasing tissue extraction and quality for corneas, among others, is planned.

Looking ahead – what next?

Following the acquisition of the licenses from Tissue Regenix, this year applications will be submitted to the Paul-Ehrlich-Institut in Langen to receive the distribution allowances for the supply of patients with corneas, heart valves and blood vessels processed with the conventional and innovative production procedures. The preliminary work and studies necessary for the application for the new technologies (dCELL®) will be finalized. “In the coming year we want to start production of more tolerable grafts and provide them for implant in the first patients,” says Nitschke.

The tissue bank's work is based on a functioning donor programme and cooperation with tissue banks. Partnerships are to be entered into with other facilities. A further ten employees are to be gradually added to the current team of seven.

The tissue bank in the Biomedical Research Centre in Rostock has at its disposal approximately 90 square metres of production space in cleanroom class A-D. With rising production capacity the production facility will be too small in around three years' time. The development of further cleanroom capacities is at the planning stage.

“Educational work and transparency in our handling of human donations is an important concern for us,” emphasise the tissue bank's CEOs, Nitschke und Odell. “Among other things, GBM-V will set up a scientific advisory board with wide-ranging control rights. The members of this board will be experts in the fields of ophthalmology, general surgery and cardiovascular surgery. Trust forms the basis of our work. We want to be very careful in our handling of this precious asset right from the beginning.”

Background information

Tissue medicine represents an important subsection of transplantation medicine. It is estimated that over 52,000 tissue transplants are performed in Germany every year, far more than organ transplants. In 2015 3.083 patients received a donor organ.
In contrast to organs, tissues are not transplanted immediately. High-quality tissue grafts are produced from tissue preparations in tissue banks. It is primarily eye corneas, heart valves, bones, tendons and fascias, as well as blood vessels and skin, that are used as tissue grafts in medicine.

In Germany there are currently approx. 26 tissue banks with a permit for postmortem tissue retrieval. Donor programmes are organised by universities (11), non-profit organisations (6) or limited-liability companies. The Gewebebank Mecklenburg-Vorpommern collaborates with gGTM-V in tissue donations.

Most important tissue donations

Tissue grafts primarily lead to improved quality of life and the faster social reintegration of patients, return to work and save lives in emergency situations.

Heart/heart valves
Damage to the heart valves is the result of calcification, infections or heart attacks. Damage is rarely congenital. Over the long-term, damaged heart valves can lead to functional weaknesses of the heart that can dramatically reduce the potential of the person affected. Possible treatments are the repair of the heart valve through a surgical procedure or the replacement of the heart valve by a prosthesis or homograft.

Blood vessels
The stenosis or a complete occlusion of blood vessels by deposits over the course of one's life can be particularly dangerous for the heart and extremities (legs). In the heart, occlusions can lead to a heart attack. In the legs, stenotic or occluded blood vessels lead to pain and restricted movement, with a risk of amputation in extreme cases. Vascular surgery uses human blood vessels to replace stenotic or occluded vessels (bypass operation). Grafts are likewise used for vessel reconstruction, and primarily in the replacement of infected plastic prostheses. Lastly come often life-saving emergency procedures.

Tendons and ligaments
Tendons and ligaments are transplanted in order to maintain and/or restore the stability and mobility of joints and to prevent artificial stiffening of the joints. Bone material replaces lost tissue following, inter alia, accidents or tumour operations and protects patients from amputations. Rare, but essential, is the use of the connective covering of the anterior thigh muscle (fascia lata) for the immediate, operative resolution of, for example, congenital defects of the abdominal wall in new-borns.

Eye donation
The cornea of the eye is also known as the eye's wind shield. An equally curved and completely clear cornea leads to clear vision. Diseases of the cornea (corneal curvature or opacity) can have a variety of causes and, if left untreated, lead to blindness via loss of clarity of vision. Corneal grafts (ceratoplastia) can protect patients from blinding or restore their vision. In this procedure, the patient's diseased cornea, or parts thereof, is replaced by a donor cornea.

Skin
The skin is the largest organ in the human body. Skin grafts are often required for patients with serious, large-area skin defects, e.g. following burning and with chronic wounds that do not heal. With large-area burns (>70 % of body area), skin grafts can save the patient's life. Soft-tissue loss due to tumours and hernias are treated successfully through skin preparations.

For further information, see http://www.organspende-info.de/organ-und-gewebespende/organe/gewebe

25 years of experience in transplant medicine

Dr. med. Frank-Peter Nitschke is a native of Rostock and studied human medicine in the city. This was followed by specialist training at the Clinic and Polyclinic for Urology at the University of Rostock , where Dr. Nitschke worked as a urologist from 1995 to 2000. Between 1992 and 2000 he also worked as Coordinator for Organ Donations and Transplantation at the Clinic and Polyclinic for Urology of the University of Rostock for the Federal State of Mecklenburg-Vorpommern, and subsequently from 2000 to 2007 as Medical Coordinator of the German Organ Transplantation Foundation (DSO) for Mecklenburg-Vorpommern. Starting in 2003, Dr. Nitschke organised the set-up of the organ donation system for Mecklenburg-Vorpommern (DSO-G). From 2007 to 2015 he worked as Medical Director of the Deutsche Gesellschaft für Gewebetransplantation (DGFG). Since 2015 he has been the head doctor of the Gesellschaft für Transplantationsmedizin Mecklenburg-Vorpommern (GTM-V) gGmbH and CEO of the Gewebebank Mecklenburg-Vorpommern (GBM-V) gGmbH.

Dr. med. Axel Manecke also studied human medicine at the University of Rostock and received his specialist training at the Clinic and Polyclinic for Urology of the University of Rostock. A native of Rostock, between 1998 and 2000 he was also Coordinator for Organ Donations and Transplantation at the Clinic and Polyclinic for Urology of the University of Rostock for the Federal State of Mecklenburg-Vorpommern, and from 2000 to 2008 as Medical Coordinator of the German Organ Transplantation Foundation (DSO) for Mecklenburg-Vorpommern. Starting in 2003 he set up the organ donation system for Mecklenburg-Vorpommern together with Dr. Nitschke. A urologist and experienced transplantation specialist, between 2008 and 2015 he worked as Regional Manager for Tissue Donation in Mecklenburg-Vorpommern for the Deutsche Gesellschaft für Gewebetransplantation (DGFG). Like Dr. Frank-Peter Nitschke, the 46 year-old is head doctor of the Gesellschaft für Transplantationsmedizin Mecklenburg-Vorpommern (GTM-V) gGmbH.

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