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    Home > Biochemistry News > Biotechnology News > 3D-engineered human tissue successfully restores walking ability in chronically paralyzed mice for the first time

    3D-engineered human tissue successfully restores walking ability in chronically paralyzed mice for the first time

    • Last Update: 2022-03-08
    • Source: Internet
    • Author: User
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    The next phase of the study - a human spinal cord implant to treat paralysis
    .
    [Sagol Center for Regenerative Biotechnology]

    The researchers, led by a team in the laboratory of Dr.
    Tal Dvir, Professor, Tel Aviv University, are now preparing for clinical trials in human patients

    .
    They hope that within a few years, the engineered tissue will be implanted in paralyzed people, allowing them to stand and walk again

    .

    (From left to right): Dr.
    Yona Goldshmit, Prof.
    Tal Dvir and Lior Wertheim [Sagol Centre for Regenerative Biotechnology]

    Dvir said: "This is the world's first example of an animal model implanted with engineered human tissue that has a restorative effect on long-term chronic paralysis, the most relevant model for the treatment of paralysis in humans
    .
    There are thousands of people around the world.
    Paralyzed due to spinal cord injury, and a condition that still has no effective treatment.
    .
    .
    we hope to reach clinical trials, in the next few years, and ultimately rehabilitate these patients

    .
    "

    The researchers published their findings in the journal Advanced Science, titled: "Regeneration of injured spinal cord during chronic phase by engineering iPSCs-derived 3D neuronal networks
    .
    "

    The authors note that traumatic spinal cord injury (SCI) has an immediate and catastrophic impact on all aspects of a patient's health and quality of life
    .
    Primary injury results in direct damage, often resulting in cell death, disruption of the blood-spinal cord barrier, and extracellular matrix (ECM) degradation

    .
    "These processes trigger a secondary pro-inflammatory injury cascade that leads to progressive tissue damage and eventual formation of glial scarring," the team continued

    .
    Healthy nerve tissue surrounding the injury site contains clues that can promote tissue repair, but the scar lacks what the researchers call a "permissive microenvironment" for cell growth and lacks ECM-secreted factors that can direct nerve growth, resulting in very poor regeneration Potential and permanent neurological dysfunction

    .

    The team further noted that cell therapy using induced pluripotent stem cell-derived neurons is considered a promising approach to regenerate injured spinal cords
    .
    "However, scar formation during the chronic phase is not a permissive microenvironment for cell or biomaterial transplantation or tissue assembly

    .
    A specific spinal cord motor neuron differentiation protocol in a 3D dynamic microenvironment.
    .
    .
    can provide clues not only for cell differentiation, but also for appropriate tissue Formation provides a natural signature signal

    .
    We further hypothesized that assembling a functional neuronal network prior to implantation would increase the chance of functional implantation

    .
    "

    There are tissue samples in the petri dish
    .
    [Sagol Center for Regenerative Biotechnology]

    In their newly published paper, the researchers describe how they recently developed iPSCs-derived human tissue implants that have the potential to perfectly match a patient's immune and cellular characteristics
    .
    They explain: "In principle, in this approach, a small piece of adipose tissue is biopsied from a patient and the cellular and acellular material are separated

    .
    When the cells are reprogrammed into induced pluripotent stem cells, the ECM is processed into Personalized hydrogels

    .
    "

    "Our technique is based on taking a small slice from a patient's abdominal fat tissue," Dvir said
    .
    This tissue, like all tissue in our body, is made up of cells and the ECM (made up of things like collagen and sugars)

    After isolating the cells from the stromal cells in vitro, we use genetic engineering techniques to reprogram the cells back to a state similar to embryonic stem cells—cells that can become any type of cell in the body
    .
    Personalized hydrogels are made in the ECM that do not cause an immune response or rejection upon implantation

    .
    We then encapsulate the stem cells in the hydrogel, and in a process that mimics embryonic development of the spinal cord, we convert the cells to contain 3D implants of neuronal networks of motor neurons

    .
    "

    Magnetic resonance imaging of spinal cord injury versus untreated
    .
    [Sagol Center for Regenerative Biotechnology]

    The authors further noted, "During the entire in vitro culture period, the cells and the hydrogel exhibited a synergistic effect, mimicking the process of spinal cord formation in embryos
    .
    The treated hydrogel supports human induced pluripotency by providing an adequate microenvironment for the cells.
    Efficient 3D differentiation of stem cells

    .
    Subsequently, during differentiation, cells at different developmental stages continuously remodel the hydrogel by secreting specific neuronal ECM proteins, providing an inducible microenvironment for cell-cell and cell-matrix interactions

    .
    "

    The resulting human spinal cord implants were tested in a paralyzed mouse laboratory model
    .
    As a proof of concept, the researchers successfully tested the implant for the first time in a mouse model of acute injury and prolonged paralysis

    .
    The team wrote: "The implant enriches the blocked area with biochemical and mechanical signals to attract progenitor cells, support cell survival and engraftment, reduce inflammation and gliosis at the lesion site, and improve overall survival in the treated animals.
    athletic ability

    .
    "

    They also tested the implant on mouse models of chronic or long-term injury and paralysis, the equivalent of a year in humans
    .
    The authors state: "After demonstrating the ability of the implants to restore the injured spinal cord during the acute phase, we went on to evaluate their ability to regenerate tissue in a more clinically relevant model

    .
    At this stage, the scar is fully developed and spontaneous recovery of behavior reaches The plateau phase was reached

    .
    " The results confirmed that 100% of the acute paralysis model and 80% of the chronic paralysis model regained the ability to walk after implantation

    .

    "These model animals undergo a rapid recovery process and eventually they can walk well.
    .
    .
    Millions of people around the world are paralyzed due to spinal cord injuries for which there is still no effective treatment

    .
    People injured at a very young age are doomed To spend the rest of your life in a wheelchair, bearing all the social, economic and health costs

    of paralysis.
    Our goal is to produce individualized spinal cord implants for each paralyzed person, allowing the regeneration of damaged tissue without rejection risk of reaction

    .

    Spinal cord treatment images
    .
    [Sagol Center for Regenerative Biotechnology]

    In their published paper, the authors conclude: "Going forward, after overcoming stringent regulatory challenges, the reported technique may be relevant for the treatment of paralyzed human patients
    .
    In this concept, a small biopsy is obtained by taking a small piece of the patient.
    tissue, it is possible to produce personalized hydrogels and generate patient-specific iPSCs to obtain personalized SC implants

    that can replace excised scar tissue and reconnect injured human SCs, potentially represents a new approach to personalized cell therapy
    .
    "

    Dvir has partnered with industry partners to form Matricelf, which is applying this approach with the goal of enabling spinal cord implant therapy for paralyzed patients
    .
    "The company's preclinical program has been discussed with the FDA," Dvir said

    .
    "Now that we've presented an advanced technology in regenerative medicine, and there are currently no other alternatives for paralyzed patients, we have every reason to expect our technology to be approved relatively quickly

    .

    Regenerating the injured spinal cord at the chronic phase by engineered iPSCs-derived 3D neuronal networks

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