Stem Cell Biology group : differentiation potential and applications for Regenerative Medicine.

Research Focus:

Our research focuses on the biology of stem cell populations, and on the mechanisms regulating their differentiation in health and disease, in order to develop new approaches for regenerative medicine.

Stem cells are the focus of intense research to understand their specific biology, in order to develop new medical treatments. The control of stem cell commitment and multipotency is a pre-requisite for their fruitful therapeutic use. We study stem cells present in postnatal & adult tissues, to investigate their regulation and their differentiation potential for biomedical applications which include new drug screening, disease modelling, tissue engineering and regenerative medicine.

Stem cell models in use include human and mouse cell cultures, from healthy and disease backgrounds including cancer models. Through a combination of cell culture in 2D and 3D, gene expression analysis and tissue engineering techniques, we are involved in a range of research projects including the regulation of neural stem cells present in different brain locations, the role of adipogenic stem cells in obesity and metabolic health, and the improvement of tissue repair processes through the use of novel biomaterials to support stem cell-based regeneration. We are also investigating the relationship between stem cells, tissue repair and neoplasia.

Research Questions:

Ÿ             Characterising stem cell populations:

Analysis of progenitor cells present in tissues, study of the distribution, cell properties, markers, differentiation capacity and gene expression pattern of stem cells to determine their core features and therapeutic potential. Development of new non-invasive techniques to monitor stem cell phenotype in vitro. Comparison of stem cells in health and disease models, including neoplasia.

Ÿ             Modelling stem cell differentiation:

Culture, expansion and differentiation of stem cells to identify the key factors involved in the acquisition of a specific lineage identity. Identification of new regulatory transcripts and pathways. Comparison of stem cell populations that remain in tissues throughout life, from different ages and disease states, refining protocols to control their cell behaviour in vitro and in vivo.

Ÿ             Driving stem cells to repair tissues:

Establishing differentiation models in 2D and in 3D, including in combination with novel biomimetic biomaterials to drive the differentiation of stem cells towards tissue repair and promote regeneration mechanisms. Contribution to several collaborative projects developing new stem cell approaches for skeletal repair. For any queries on our research, please contact virginie.sottile@unipv.it.

Projects in our group include:
Paola Fulghieri studies the role of cell differentiation pathways in cancer outspreading, using models of cancer and stem cells in vitro, in collaboration with the group of Prof L. Stivala.

Lidia Pollara develops new in vitro models to study the molecular basis of Joubert syndrome (JS) in collaboration with Prof EM Valente, using patient-derived induced pluripotent stem cells (iPSCs) to analyse disease-specific changes in mechanisms such differentiation, migration and

Recent Papers from our group (last 6 years):

•  De Melo N, Murrell L, Islam M T, Titman JJ, Macri-Pellizzeri L, Ahmed I, Sottile V. (2021) Tailoring pyro- and orthophosphate species to enhance stem cell adhesion to phosphate glasses. Int. J. Mol. Sci. 22(2):837. doi: 10.3390/ijms22020837
•  Dell’Olio F, Su J, Huser T, Sottile V, Cortés-Hernández LE, Alix-Panabières C. (2021) Photonic technologies for liquid biopsies: recent advances and open research challenges. Laser & Photonics Reviews 15(1): 2000255. doi:10.1002/lpor.202000255.
•  Omar A Hamid OA, Eltaher HM, Sottile V, Yang J. (2020) 3D Bioprinting of a stem cell-laden, multi-material tubular composite: an approach for spinal cord repair. Mat Sci Eng C. 120:111707. doi:10.1016/j.msec.2020.111707.
•   Velickovic K, Lugo Leija AL, McGinlay S, Symonds ME, Sottile V. (2020) New models of adipogenic differentiation highlight a cell-autonomous response to temperature. Biocell 44(4):501-512. doi: 10.32604/biocell.2020.012942.
•   Ahmad A, Strohbuecker S, Scotti C, Tufarelli C, Sottile V. (2020) In silico identification of SOX1 post-translational modifications highlights a shared protein motif. Cells 9, 2471. doi: 10.3390/cells9112471.
•   Lugo Leija HA, Velickovic K, Bloor I, Sacks H, Symonds ME, Sottile V. (2020) Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia. J Cell Mol Med 24(19):11434-11444. doi: 10.1111/jcmm.15749.
•   Velickovic K, Lugo Leija AL, Surrati A, Kim DH, Sacks H, Symonds ME, Sottile V. (2020) Targeting glutamine synthesis inhibits stem cell adipogenesis in vitro. Cell Phys Biochem 54:917-927. doi: 10.33594/000000278.
•  De Melo N, McGinlay S, Markus R, Macri-Pellizzeri L, Symonds ME, Ahmed I, Sottile V. (2019) Live Simultaneous Monitoring of Mineral Deposition and Lipid Accumulation in Differentiating Stem Cells. Biomimetics 4(3), 48. doi.org/10.3390/biomimetics4030048.
•  Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. (2019) Velickovic K, Wayne D, Lugo Leija HA, Bloor I, Morris D, Law J, Budge H, Sacks H, Symonds M, Sottile V. Sci. Rep. 9(1):9104. doi: 10.1038/s41598-019-45540-1.
•  Harrison R, Luckett J, Marsh S, Lugo Leija HA, Salih S , Alkharji R, Sottile V. (2019) Magnetically assisted control of stem cells applied in 2D, 3D and in situ models of cell migration. Molecules 24(8). pii: E1563. doi:10.3390/molecules24081563.
•  McLaren J, Macri Pellizzeri L, Hossain KMZ, Patel U, Grant D, Scammell B, Ahmed I, Sottile V. (2019) Porous phosphate-based glass microspheres show biocompatibility, tissue infiltration and osteogenic onset in an ovine bone defect model. ACS Applied Materials & Interfaces 11(17):15436-15446. doi: 10.1021/acsami.9b04603.
•  Prosser A, Scotchford C, Roberts G, Grant D, Sottile V. (2019) Integrated Multi-Assay Culture Model for Stem Cell Chondrogenic Differentiation. Int. J. Mol. Sci. 2019, 20(4), 951. https://doi.org/10.3390/ijms20040951.
•  Patel U, Macri-Pellizzeri L, Hossain KMZ, Scammell BE, Grant DM, Scotchford CA, Hannon AC, Kennedy AR, Barney ER, Ahmed I*, Sottile V*. (2019) In vitro cellular testing of Strontium/Calcium substituted phosphate glass discs and microspheres shows potential for bone regeneration. J Tissue Eng Regen Med. 2019;1–10. doi: 10.1002/term.2796.
•  Harrison RP, Chauhan VM, Onion D, Aylott JW, Sottile V. (2019) Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells. RSC Adv. 9(6):3176-3184. doi: 10.1039/c8ra09089k.
•  Nizamudeen Z, Markus R, Lodge R, Parmenter P, Platt M, Chakrabarti L, Sottile V (2018) Rapid and accurate analysis of stem cell-derived extracellular vesicles with super resolution microscopy and live imaging. Biochim Biophys Acta Mol Cell Res. pii: S0167-4889(18)30412-9. https://doi.org/10.1016/j.bbamcr.2018.09.008.
•  Nizamudeen Z, Markus R, Lodge R, Parmenter P, Platt M, Chakrabarti L, Sottile V. Rapid and accurate analysis of stem cell-derived extracellular vesicles with super resolution microscopy and live-imaging. BBA Molecular Cell Research 1865(12):1891-1900. doi: 10.1016/j.bbamcr.2018.09.008.
•  Harrison R, Lugo Leija HA, Strohbuecker S, Crutchley J, Marsh S, Denning C, El Haj A, Sottile V. (2018) Development and Validation of Broad-Spectrum Magnetic Particle Labelling Processes for Cell Therapy Manufacturing. Stem Cell Research & Therapy 26;9(1):248. doi: 10.1186/s13287-018-0968-0.
•  Velickovic K, Lugo-Leija HA, Bloor I, Law J, Sacks H, Symonds M, Sottile V. (2018) Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro. Sci Rep. 8(1):4974. doi: 10.1038/s41598-018-23267-9.
•  Nizamudeen ZA, Chakrabarti L, Sottile V. (2018) Exposure to the ROCK inhibitor fasudil promotes gliogenesis of neural stem cells in vitro. Stem Cell Res 28: 75-86.  doi:10.1016/j.scr.2018.02.001.
•  Macri-Pellizzeri L, De Melo N, Ahmed I, Grant D, Scammel B, Sottile V. (2018) Live quantitative monitoring of mineral deposition in stem cells using tetracycline hydrochloride. Tissue Eng Part C 24(3):171-178. doi: 10.1089/ten.TEC.2017.0400.
•  Gupta D, Grant DM, Hossain KMZ, Ahmed I, Sottile V. (2018) Role of geometrical cues in bone marrow derived mesenchymal stem cell survival, growth and osteogenic differentiation. J Biomater Appl. 32(7):906-919. doi: 10.1177/0885328217745699.
•  Ahmad A, Strohbuecker S, Tufarelli C, Sottile V. (2017) Expression of a SOX1 overlapping transcript in neural differentiation and cancer models. Cell Mol Life Sci. 74(22):4245-4258. doi: 10.1007/s00018-017-2580-3.

A full list of our publications can be found here.