HYBRID EVENT: You can participate in person at Rome, Italy or Virtually from your home or work.

4th Edition of International Conference on Tissue Engineering and Regenerative Medicine

September 19-21 | Rome, Italy

September 19 -21, 2024 | Rome, Italy
TERMC 2023

Panagiotis Mallis

Panagiotis Mallis, Speaker at Tissue Engineering Conferences
Biomedical Research Foundation Academy of Athens, Greece
Title : Immunomodulatory and regenerative properties of mesenchymal stromal cells: Can we improve their abilities?

Abstract:

Accumulated evidence has emerged on the role of stem cells in key cellular functions such as their implication in host immune response and tissue regeneration. Currently, Mesenchymal Stromal Cells (MSCs), which are multipotent stem cells, have been used in a great number of clinical trials (> 1300 studies, worldwide), ensuring the safety and tolerability of these cells in several human disorders, such as autoimmune diseases, graft versus host disease (GvHD) and cancer. Lately, well-defined MSCs were used for the toleration of the acute immune response and cytokine release syndrome in severely ill COVID-19 patients. However, significant differences have been reported regarding immune modulation and tissue regeneration exerted by the MSCs. Late evidence has shown that inborn errors of immunity and the presence of different Human Leukocytes Antigens (HLA) may either prevent or promote the beneficial properties of MSCs towards human disorders. This study aimed to the evaluation of the immunomodulatory and regenerative properties of MSCs by comprehensively investigating the HLA alleles. MSCs derived from the human Wharton's Jelly (WJ) tissue and bone marrow (BM) were isolated, cryopreserved, expanded, and defined according to the criteria outlined by the International Society for Cell and Gene Therapies (ISCT). WJ and BM-MSCs were stimulated with a culture medium containing IFN-γ (50 ng/ μl), 1% penicillin-streptomycin, and 1% L-glutamine for 48 h. The quantification of IL-1Ra, IL-6, IL-10, IL-13, TGF-β1, VEGF-a, FGF, PDGF, and IDO was performed using ELISA kits. The expression of HLA-G1, G5, and G7 was evaluated in WJ and BM-MSCs. The determination of the HLA alleles of the MSCs was performed using the Next Generation Sequencing technology (HLA Holotype 11 loci, Omixon Inc., MiSeq, Illumina). The frequencies of the HLA alleles were estimated using the Arlequin and MEGA X software. Thawed WJ and BM-MSCs exhibited a spindle-shaped morphology, successfully differentiated to "osteocytes", "adipocytes", and "chondrocytes", and in flow cytometric analysis were characterized by positivity for CD73, CD90, and CD105 (> 95%) and negativity for CD34, CD45, and HLA-DR (< 2%). Moreover, stimulated WJ and BM-MSCs were characterized by increased cytoplasmic granulation, in comparison to unstimulated cells. The HLA-G isoforms (G1, G5, and G7) were successfully expressed by the unstimulated and stimulated WJ-MSCs. On the other hand, only weak expression of HLA-G1 was identified in BM-MSCs. Stimulated MSCs secreted high levels of IL-1Ra, IL-6, IL-10, IL-13, TGF-β1, FGF, VEGF, PDGF, and IDO in comparison to unstimulated cells (P < 0.05) after 12 and 24 h. Finally, macrophages derived from COVID-19 patients successfully adapted the M2 phenotype after co-culturing with stimulated WJ and BM-MSCs. Also, the most frequent HLA alleles were determined, to identify potential correlation with the MSCs? immunomodulatory and regenerative properties. Specific HLA alleles were correlated positively with the MSCs? immune responses and regenerative properties. In this way, the establishment of a stem cell bank with specific MSCs lines may be performed, in order properly defined MSCs to be used for specific patients, thus bringing precision medicine one step closer to its clinical application.

Audience Take Away:

  • Present the current status of Mesenchymal Stromal Cells
  • Present modern mechanisms regarding the immunomodulatory/ immunoregulatory role of MSCs
  • Evaluation of immunoregulatory properties between fetal and adult MSCs
  • Discuss the specific mechanism of action, through which the MSCs can exhibit their beneficial properties in immune-related disorders.

Biography:

Panagiotis Mallis gained his bachelor degree (BSc) in Biomedical Sciences from the Athens University of Applied Sciences in 2010. In 2013, he received his master diploma (MSc) and in 2018, received his PhD in Tissue Engineering and Regenerative Medicine from the Medical School of National and Kapodistrian University of Athens. Currently, Mallis Panagiotis is member of the Hellenic Cord Blood Bank (HCBB). Panagiotis Mallis has extensive experience in mesenchymal stromal cell (MSCs) isolation and in vitro manipulation. His current research involves the investigation of MSCs’ immunoregulatory/immunosuppressive properties and their applicability in tissue engineering and regenerative medicine approaches.

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