Characterization of the interaction between the immune system and the extracellular matrix in cardio-muscular and neurodegenerative pathologies
The research group is involved in the field of regenerative medicine developing approaches that concern genetic correction or modulation of epigenetic factors supported by the most recent advances in cell therapy. To date, the progresses offered by induced pluripotent stem cell (iPSC) technology, in the field of regenerative medicine, have not been able to fully express their potential due to limited technologies bearing them. Our strategic approach exploits the capability of these cells to generate in vitro human tissues belonging to specific individuals, for advanced investigations in the personalized medicine field, sustaining them with innovative technologies, such as biomaterials and 3D bio-printing. The scientific commitment benefits of cutting-edge technologies in the bio-medical and personalized medicine field to improve the knowledge of cardio/muscular and neurodegenerative pathologies, with the aim of developing a standardized platform for the in-depth study of patient-specific organ models.
Genetic disorders, such as Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis, present similarities related to the ability of the immune system cells in conditioning the extracellular matrix in response to the request of pathophysiological remodelling. In particular, the accumulation of specific factors, such as chondroitin sulphate proteoglycans (CSPGs), in the extracellular matrix showed a high inhibitory connotation for neuromuscular innervation. The denervation, caused by the accumulation of CSPGs released by activated immune cells into the interstitial space, leads, either at the muscular or spinal cord level, to a cascade of extremely damaging events for the organism, such as the total absence of voluntary control until the death of the individual. Recently, we have developed an innovative approach employing a bio-ink, derived from decellularized “sick” organs, to recapitulate the endogenous substrate typical of pathological tissues, in which different cell lines derived from iPSC can be bio-printed to characterize their behaviour and the intercellular relationships.
Preliminary data, emerged from our recent experimentation, allow to affirm that mimicking the components of the extracellular matrix can represent the added value to recapitulate the right structures and characteristics of human organs on which the effects of new drugs or innovative therapeutic approaches can be analysed. Indeed, the perturbation of CSPGs secreted in the extracellular matrix or the inhibition of the specific PTPRS receptor, showed an improvement in nerve conduction and a significant slowing in the progression of neurodegenerative pathologies.
The ambition of the laboratory is to act as accelerator of practical knowledge to guarantee an early diagnosis and to support the advanced treatment of diseases that, until now, included invasive investigations on patients.
- Effect of the chondroitin sulfate proteoglycan-4 secreted by macrophage/fibroblast crosstalk on sympathetic cardiac denervation in Duchenne Muscular Dystrophy.
- Generation of individual-specific human tissues for efficacy testing of new drugs.
- Development of a 3D bio-printed patient-specific neuromuscular junction for the in-depth study of the immunomodulatory role of Mir 125b in the onset and progression of amyotrophic lateral sclerosis.
- Sp1 acetylation function in the regulation of CSPG4/PTPσ axis during sympathetic cardiac re-innervation in Duchenne Muscular Dystrophy.
- Role of histone deacetylase inhibitor (HDAC) givinostat on cardiac remodeling.
- A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes.
Maiullari F, Costantini M, Milan M, Pace V, Chirivì M, Maiullari S, Baci D, Marei HE, Seliktar D, Rainer a, Gargioli C, Bearzi C, Rizzi R.
Sci Rep. 2018 Sep 10;8(1):13532. doi: 10.1038/s41598-018-31848-x.
- Givinostat reduces adverse cardiac remodeling through regulating fibroblasts activation.</strong
Milan M, Pace V, Maiullari F, Chirivì M, Baci D, Maiullari S, Madaro L, Maccari S, Stati T, Marano G, Frati G, Puri PL, De Falco E, Bearzi C, Rizzi R.
Cell Death Dis. 2018 Jan 25; 9(2):108.
- Potential of stem cell-based therapy for ischemic stroke.
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- Role of the Gastrointestinal Tract Microbiome in the Pathophysiology of Diabetes Mellitus.
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- Biphasic effects of propranolol on tumour growth in B16F10 melanoma-bearing mice.
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- Down regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells.
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- Self-assembled polydimethylsiloxane structures from 2D to 3D for bio-hybrid actuation.
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- In vivo generation of an artificial, functional skeletal muscle.
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- DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation.
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- 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering.
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- Human placenta-derived neurospheres are susceptible to transformation after extensive in vitro expansion.
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- PlGF-MMP9-engineered cardiomyocyte-derived iPS cells supported on a PEG-fibrinogen hydrogel scaffold possesses an enhanced capacity to repair damaged myocardium.
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- The RNA binding protein ESRP1 fine-tunes the expression of pluripotency-related factors in mouse embryonic stem cells.
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- A collagen membrane-based engineered heart tissue improbe cardiac function in ischemic rat hearts.
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- Tissue engineering for skeletal muscle re generation.
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- Post-natal cardiomyocytes can generate iPS cells with an enhanced capacity toward cardiomyogenic re-differentiation.
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Cell Death Differ. 19:1162-74, 2012.
- MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice.
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