**Background:** The 2022 Italian Mesenchymal Stem Cell Group (GISM) Annual Meeting, held on 20–21 October 2022 in Turin, Italy, brought together researchers and clinicians to discuss the latest advances in mesenchymal stem/stromal cell (MSC) research. The meeting was structured around six new sections reflecting the evolving interests of the GISM community: (1) Bringing advanced therapies to the clinic, (2) GISM Next Generation, (3) New technologies for 3D culture systems, (4) Therapeutic applications of MSC-EVs in veterinary and human medicine, (5) Advancing MSC therapies in veterinary medicine, and (6) MSCs: a double-edged sword in oncology. The goal was to promote interactive discussion and training, particularly for younger researchers.
**Methods:** The meeting featured invited talks and selected oral communications from national and international speakers. Each session included at least 30 minutes for questions and discussion. Over 100 researchers participated, and 51 posters were presented. Three Young Investigator Awards of 500 euros each were awarded to Priscilla Berni, Elena Ceccotti, and Gianluca Cidonio. The report summarizes key presentations from each session, covering topics such as regulatory approval of ATMPs, funding gaps, 3D culture models, EV characterization, veterinary applications, and the dual role of MSCs in cancer.
**Key Results:**
- **Session 1:** Graziella Pellegrini presented Holoclar, the first stem cell-containing ATMP to receive EMA marketing authorization (2015) for limbal stem cell deficiency, based on a confirmatory trial of 80 patients and follow-up from 1997 to 2008. Stefano Cosma analyzed 12,934 interventional studies from Italy and 1137 from Europe, highlighting correlations between funding sources and clinical trial success. Nicholas Crippa Orlandi showed that MSCs on SmartBone scaffolds differentiated into osteoblasts and produced collagen. Ilaria Roato compared MSCs from different oral cavity sites, finding that SHED and DPSCs had a higher percentage of endothelial precursors than PDLSCs. Marta Nardini developed a potency assay using Gold-Nanostars and Optoacoustic Imaging, showing that GNs reached all organs after one day in NuNu mice but could not overcome the blood-brain barrier.
- **Session 2:** Focused on publishing, patents, and fundraising. Filippo Piccinini discussed journal selection and impact factors. Paola Bagnoli described the role of Technology Transfer Offices in protecting intellectual property. A roundtable with senior researchers discussed fundraising opportunities for MSC research.
- **Session 3:** Matteo Moretti presented a joint-on-a-chip model that recapitulated osteoarthritis hallmarks and tested MSC effects. Maria Harmati tracked EV-mediated crosstalk in 3D tumour models of ductal carcinoma, melanoma, and osteosarcoma. Lucia Ceresa demonstrated an ATP-based rapid microbial detection method (Celsis) for cell-based products. Silvia Scaglione presented the MIVO organ-on-chip platform, showing that a 3D ovarian model treated with Cisplatin in MIVO had similar tumour regression to xenograft models, while static culture showed unpredicted chemoresistance.
- **Session 4:** Stefania Bruno discussed hurdles in translating MSC-EV therapy to the clinic, emphasizing the need to define the mode of action. Silvia Zia presented the Celector instrument for ATMP quality control, capable of separating cells based on physical characteristics in about 15 minutes. Elena Ceccotti showed that human liver stem cell EVs attenuated kidney damage in AKI mice by reducing tubular necrosis and increasing tubular cell proliferation, and in CKD mice, they reduced interstitial fibrosis and pro-fibrotic gene expression. Tarlan Eslami Arshaghi developed a fluorescence polarization-based EV quantification method using aptamers. Enrico Ragni characterized ASC secretome, finding over 50 cytokines/chemokines and more than 200 EV-miRNAs, with inflammatory preconditioning increasing its ability to modulate inflammation and degeneration.
- **Session 5:** Laura Barrachina Porcar discussed allogeneic MSC immunogenicity and immunomodulation, proposing haplo-banks of MHC-homozygous donors. Barbara Merlo showed that the α4β1 integrin agonist GM18 affected equine MSC adhesion to PLLA scaffolds, with Wharton's jelly MSCs being more suitable than adipose-derived MSCs. Gabriele Scattini described migrasomes, a distinct type of EV released by MSCs, with diameters of 500–2000 nm.
- **Session 6:** Roisin Dwyer presented MSC-EVs enriched with tumour suppressor microRNA for breast cancer therapy. Andrea Papait discussed the dual role of MSCs in the tumour microenvironment, noting they can serve as drug carriers but also participate in tumour initiation and progression. Valentina Coccè showed that micro-fragmented adipose tissue (MFAT) loaded with paclitaxel produced a dose-dependent inhibition of human mesothelioma cell line MSTO-211H in vitro and reduced tumour mass volume in xenografted Balb/c-Nude mice, similar to free PTX.
**Clinical Implications:** The meeting underscored the progress and challenges in translating MSC-based therapies. The successful EMA approval of Holoclar provides a model for regulatory pathways for ATMPs. The development of 3D culture systems like joint-on-a-chip and MIVO platforms offers tools for personalized therapy testing and drug screening, potentially reducing reliance on animal models. MSC-EVs show promise as cell-free therapeutics for kidney disease, osteoarthritis, and cancer, but standardization and understanding of mechanisms are critical. In veterinary medicine, MSCs may offer alternatives to surgery for conditions like cranial cruciate ligament rupture. The dual role of MSCs in oncology highlights the need for careful consideration in cancer applications, with potential for drug delivery but risks of promoting tumour progression. Overall, the meeting emphasized the importance of funding, regulatory science, and interdisciplinary collaboration to advance MSC therapies from bench to bedside.