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Apr 1, 2012 (Vol. 32, No. 7)

Regenerative Medicine Looks to the Future

  • Velocity, Key to Tissue Biopreservation

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    A scientist at Core Dynamics demonstrates the operation of one of the company’s directional solidification, multithermal vertical freezing systems, which are based on technology similar to that found in multithermal gradient instruments.

    According to Sachi Norman, M.D., CEO of Core Dynamics, the firm’s goal with the use of the Multi-Thermal Gradient (MTG)™ freezing technology is to bring the “science fiction” of cryopreservation into the clinical reality of regenerative medicine.

    The precise temperature control needed to properly freeze and store tissue is extremely difficult. It often leads to a significant decrease in cellular viability in response to direct structural damage from random ice crystal formation, as well as indirect damage through changes in cellular signaling, osmotic stress, and chemical toxicity.

    MTG takes a different approach to biopreservation with the use of directional freezing. By regulating the velocity of a sample over a steady temperature gradient, well-controlled linear—rather than random—ice crystals can form, which greatly reduces the amount of structural cellular damage in frozen tissue.

    The use of toxic chemicals such as DMSO is also not necessary. In preliminary clinical trials, Core Dynamics successfully applied MTG to the clinical cryopreservation and transplantation of osteoarticular grafts into the knee, explained Dr. Norman. It also transplanted fully functional frozen/thawed ovaries, which successfully lead to embryo development in sheep.

    With a subsequent sublimation step, Core Dynamics has shown that viable frozen cells can be lyophilized and stored at room temperature. Effective reconstitution of lyophilized cells, due to an upregulation of reactive oxygen species (ROS) and other cellular stress, according to Dr. Norman, is a limiting factor; however, by optimizing the reconstitution fluid with antioxidants and other additives, cord blood stem cells were successfully lyophilized and reconstituted. They exhibited the same biochemical characteristics and increased cell viability compared to normal frozen cord blood cells.

    In collaboration with the U.S. Army, Core Dynamics is now working to lyophilize, store, and reconstitute red blood cells. Although not yet clinically viable with a blood cell viability of 70% post-reconstitution, with constant optimization, Core Dynamics is close to perfecting lyophilized blood, said Dr. Norman, which would be a major advantage for healthcare, particularly in regions of the world that cannot afford expensive storage refrigerators and freezers.

  • Tissue Engineering and Cell Therapy

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    NeoCart training sample in a petri dish. NeoCart is an ex vivo implant used to treat large ICRS type III or IV lesions of articular cartilage. [Histogenics]

    Histogenics and ProChon Biotech merged last year, combining tissue engineering with cellular therapy to develop a regenerative medicine company. Kirk Andriano, Ph.D., discussed Histogenics’ NeoCart®, and VeriCart™ technology at the meeting.

    NeoCart is an ex vivo implant used to treat large ICRS type III and IV lesions of articular cartilage. The patient’s own cartilage cells are removed and cultured in a high-pressure system that mimics the conditions in the knee while walking.

    Once surgically grafted to the damaged cartilage, the implant integrates into the native tissue and induces high-quality hyaline cartilage growth, explained Dr. Andriano. He said that in a recent two-year clinical follow-up study, NeoCart exhibited statistical superiority to microfracture surgery, the presently used gold-standard technique for damaged cartilage.

    With microfracture, surgically induced fractures in the subchondral bone plate of the knee create a blood clot, which mediates the growth of weaker fibrous cartilage. NeoCart is presently undergoing Phase III trials and the company is in negotiation with the FDA for a special protocol assessment approval.

    VeriCart, on the other hand, according to Dr. Andriano, “will augment microfracture surgery rather than completely replace it.” VeriCart is a cell-free scaffold system rehydrated with autologous bone marrow stem cells and implanted into damaged cartilage.

    When combined with microfracture surgery, VeriCart could improve growth and repair of high-quality hyaline cartilage. By using ProChon Biotech’s fibroblast growth factors that influence stem cells to differentiate into early lineage chrondocytes, Histogenics also hopes to develop a one-step procedure that bypasses invasive diagnostic joint surgery, in order to streamline cartilage repair.

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