Roberto Gramignoli

Roberto Gramignoli

Senior Research Specialist | Docent
Visiting address: Avd. Patologi, ANA Futura, Alfred Nobels alle 8, plan 8, 14152 Huddinge
Postal address: H5 Laboratoriemedicin, H5 Patologi Gramignoli, 141 52 Huddinge
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About me

  • Preclinical research and clinical program in cell-based therapies for
    regenerative medicine application, primarily for acute and congenital liver
    diseases.
    I have always been keenly investigating new, advanced treatments for liver
    disease. I started my post-graduate studies on cell-based treatments for
    liver disease in Italy, and later invited to join Dr Strom’s team
    (University of Pittsburgh Medical Center, PA-USA), the first to perform
    allogenic *hepatocyte transplantation* in patients with acute or chronic
    disorders. Working together, we promptly became the first facility to be
    approved by the US-FDA to isolate and transplant human hepatocytes. I have
    been playing prominent role in planning, developing and finalizing all the
    methodological and regulatory issues to translate cellular therapies into
    clinic, first in Italy, then in USA, and now at KI. During my PhD studies,
    I identified and proposed new solutions for several roadblocks preventing
    additional clinical results in hepatocyte transplants. Established that
    the main limiting factor in hepatocyte transplant is the availability of
    useful cells, I focused my energy to identify alternative sources for mature
    and functional hepatocytes, such as cells isolated from non-heart beating
    donors, or explanted liver tissues (‘domino liver cell strategy’), or
    fetal and neonatal human hepatocytes. All the validated cell sources were
    lately successfully translated in clinical programs (by our group and
    others’). So far, only one type of human stem cells has satisfied safety
    and efficacy requirements, rescuing life-threatening preclinical models of
    acute and congenital human liver diseases:* epithelial cells isolated from
    amnion membrane *in full-term placentae. Our group is active in translating
    such new stem cell therapy to the clinic, where for the first time we can
    inject primary allogenic stem cells without immunosuppression in support.

Research

  • Our group has always been on the front line for the treatment of acute and
    congenital liver disorders by cell-based therapies. We dedicated our
    efforts in the advancement of cell-based therapies for liver diseases, with
    *hepatocyte transplant* as a bridge or an alternative to orthotopic liver
    transplantation. Since the main limiting factor in the use of human
    hepatocyte as a clinical therapy is the availability of useful cells from
    livers deemed unsuitable for transplantation, we focused our attention on
    alternative sources, with greatest results obtained by transplantation
    of amnion epithelial cells.
    Our group was the first to report the stem cell nature and outstanding
    potential of placental *amnion epithelial *(AE) *cells*. We developed
    protocols for AE isolation and hepatic differentiation. Based on AE
    safety, technical feasibility, reduced economic cost, and the lack of ethical
    issues, we standardized protocols for AE isolation under GMP conditions, and
    efficient delivery route for clinical transplant. The use of relevant
    experimental models is of undeniable importance to examine the efficacy and
    safety of the product
  • thus, we validated the potential of AE therapy in
    different life-threatening models of liver disease. In collaboration with
    my Mentor (prof. Strom), we reported the most detailed study and correction
    of the amino acid and neurotransmitter abnormalities ever reported by a human
    stem cell. Preclinical data suggest that, although not the patient’s own
    cells, AE cells will likely not require immunosuppression. In support to
    allogenic use of AE cells without immunosuppression, during the past years we
    identified and described different molecular pathways constitutively
    expressed by these cells which may lead to a new, unlimited source of stem
    cells for regenerative medicine approaches, not only liver-specific. If
    forthcoming clinical trials bear this out, this is a paradigm shift for
    allogeneic cell transplantation, where the risk of side effects of
    immunosuppression is removed. This would allow AE therapy to be extended to
    tens of thousands of patients currently not considered for organ or cell
    transplant, as young/elder patients or congenital errors of metabolism.

Articles

All other publications

Employments

  • Senior Research Specialist, Department of Laboratory Medicine, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2022

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