Episode 22: Cells, microbes and cell therapy

00:00:00:

00:00:07: Welcome to another episode of phdbinambia in the lab.

00:00:11: Today we'll explore a fascinating world of cells, microbes and cell therapies.

00:00:16: Let's begin!

00:00:21: Hello everyone my name is Feliciana Yamibelli.

00:00:24: I'm first year PhD student at the laboratory of neurophysiology and neurobiology of developmental brain disorder Coordinated by Professor Chani.

00:00:35: My research focuses on developing a novel therapeutic platform for CDKL-V deficiency disorder, a CVRX link neurodevelopmental condition characterized by early onset epilepsy and profound cognitive and motor impairments.

00:00:53: CDD is a monogenic disorder caused by mutations in the CDKF gene leading to lack of functional proteins.

00:01:02: While protein replacement therapy is a logical approach, its clinical application is hindered by two major factors.

00:01:10: The challenge of crossing the blood-brain barrier and high cost and invasiveness for lifelong systemic administration.

00:01:19: In our laboratory we previously demonstrated that fusing the CDKLV protein with the TADSELP and RATIMPEP ties allows it to reach the brain and rescue functional defect in mouse models.

00:01:33: However, the production delivery of this recombinant protein remains significant harvest!

00:01:40: To overcome these limitations my project explores an innovative delivery system using Lactococcus Lactis.

00:01:49: This is a food grade generally recognizes safe bacterium.

00:01:55: Our goal is to engineer lactococcus lactis, too hacked as living biofactory.

00:02:03: Once administered thoroughly this engineered bacteria can produce and secrete the therapeutic protein directly in gastrointestinal tract potentially allowing for a non-invasive and continuous delivery of treatment.

00:02:19: A critical part of my work involves protein engineering.

00:02:24: The full-length CDKLV protein is highly

00:02:28: unstable

00:02:29: due to its disordered C-terminal region, which it's easily degraded by bacterium proteases.

00:02:38: To address this I have worked on the cyanotrunkated variation.

00:02:44: Among these, we identify a specific construct named DC-Five Hundred Fifty.

00:02:51: This variant maintains

00:02:52: full

00:02:53: enzymatic activity but exhibits significantly higher stability and expression level within the Lactococcus lactate system making it the ideal candidate for our delivery model.

00:03:07: Currently, we are optimizing the secretion efficiency of this e-fine hundred fifty construct.

00:03:14: The next phase on my PhD will involve vivovalidation in CDKL five knockout mice.

00:03:22: We evaluate by distribution of protein from gut to central nervous system and assess its efficacy improving behavioural and morphological phenotype.

00:03:34: In conclusion This project aimed to transform protein replacement therapy

00:03:39: from

00:03:40: an invasive procedure into a scalable, cost-effective and oral treatment.

00:03:46: If successful this microbial delivery platform could be adapted for various other genetic disorders providing a more accessible therapeutic future for patients.

00:03:58: Thank you

00:04:02: Hello everyone, my name is Lungina Urora and I'm a first-year PhD student in the Signally Transduction Laboratory coordinated by Professor Ratti.

00:04:11: My Phd project focuses on skeletal mass regeneration with particular emphasis of an innovative therapy known as photobiomodulation.

00:04:22: Muscle injuries are very common, especially in sports and during aging.

00:04:27: And they don't always heal effectively.

00:04:30: When the damage is extensive muscle tissue may lose its regenerative capacity and develop fibrosis or functional impairment.

00:04:39: For this reason it's essential to understand how to stimulate the cellular mechanism that promote proper muscle regeneration.

00:04:49: Photobium modulation is a

00:04:50: non-invasive

00:04:51: therapy that uses low intensity light in the visible or near infrared spectrum to stimulate cell activity.

00:05:00: It has already been used with promoting results skin regeneration and inflammation control, however its application in skeletal muscle still poorly explored and strong scientific evidence currently lacking.

00:05:18: The core of my project is to investigate how photobiomodulation influences the muscle microenvironment by evaluating activity of different cellular populations that compose it.

00:05:34: Particular attention gives us the so-called secretome, which is a collection of bioactive molecules produced by cells.

00:05:45: A fundamental component of the secretome is represented by a cellular bicycle, as more structure that transport proteins, growth factor and microRNAs play a key role in cell-to-cell communication.

00:06:04: The hypothesis for my work is that photobium modulation modulates the release of this SSL or bicycle, making them more effective in supporting muscle repair after injury and reducing local inflammation.

00:06:24: To study these mechanisms I will use different in vitro models.

00:06:30: In the first phase I will develop two-dimensional models of healthy and damaged skeletal muscle by inducing muscle atrophy, and subsequently applying photobium modulation using a different treatment parameters.

00:06:49: Then i'll analyze the secretome as a cell or bicycle product evaluating their molecular content regenerative potential.

00:07:00: Subsequently, I will recreate an inflammatory microenvironment by involving immune system cells in order to investigate whether photobiomodulation also exerts immunomodulatory effect.

00:07:19: Finally, the project includes the development of a three-dimensional skeletal muscle model which more closely resembles physiological muscle tissue to test the effectiveness of photobiomodulation in complex and realistic systems.

00:07:40: In conclusion this study aims to clarify the cellular and molecular mechanism underlying biomodulation, we have the goal of contributing to development a new therapeutic strategy that improves skeletal mass regeneration in a safe and non-invasive manner.

00:08:08: My name is Aretha Ramballi.

00:08:10: I'm PhD candidate at the University of Bologna.

00:08:15: Before diving into it i'd like whose contribution is helping us carry out this research.

00:08:24: Today, I'd like to share with you my research project focused on the development of a cell-based therapy for type one diabetes.

00:08:33: Type One Diabetes is an autoimmune disease in which the immune system destroys pancreatic beta cells necessary for producing insulin.

00:08:42: For patients these means life long dependence and the challenge of maintaining stable glucose levels.

00:08:50: Even with modern therapies which include the use of monoclonal antibodies and advanced devices for insulin administration, the burden remains high.

00:09:00: My project starts from a simple but ambitious question Can we create therapeutic strategies as they restore insulin production while also modulating immune system without relying on life-long immune suppression?

00:09:14: In order to answer this question, my work is based on the use of perinatal stem cells which are collected from tissues such as the amniotic membrane and umbilical cord.

00:09:24: Why these cells?

00:09:26: Because they are incredibly versatile since they combine two powerful features They can differentiate into insulin producing cells And have strong immune modulatory properties.

00:09:38: in particular The three cell types that I will focus my attention with amniotic epithelial cells isolated from the amnius, umbilical cord mesenchymis themselves isolated form the worton jelly and finally then the telus cells from the umbilic alvein.

00:09:55: My goal is to drive amniatic epithelaal cell into insulin producing cells making them responsive different glucose concentrations.

00:10:04: but how it's possible change their identity of these cells?

00:10:08: First of all is important to prime the cells, driving them into a more plastic state.

00:10:13: To do that says we undergo two specific treatments using small molecules to facilitate the differentiation process.

00:10:21: but in type one diabetes producing insulin is not enough.

00:10:25: What it's important infact is to suppress the autoimmune attack against specific antidein bodies characteristic of this pathology.

00:10:33: So how can we modulate immune system?

00:10:37: This is where umbilical cord mesenchymis and cells comes to the A. These cells in fact are well known for their capacity to modulate immune system, suppressing the cytotoxic population which is involved in beta cell destruction.

00:10:52: To really mimic what happens inside a pancreas The idea is build three dimensional structure that doesn't just look like an eyelid but actually behaves like one.

00:11:03: So we combine cells that can produce insulin with cells that modulate the immune system, and then add an endothelial population to recreate those micro vessels which keep the world's spheroid alive.

00:11:15: In the end my aim is create a vascularized immune-tolerant insulin producing spheroids that could one day offer our new therapeutic option for people living type I diabetes.

00:11:31: Hello!

00:11:32: My name is Martina Sarga.

00:11:34: I am a nurse and currently in the first year of my PhD in biomedical and neuromotor sciences.

00:11:41: The project that i'm working on is titled Optimizing Post-Transplant Outcome Through Interdisciplinary Health Sciences Intervention, A Multidimensional Approach In An Italian University Hospital.

00:11:52: The research is about post-transplant care and in particular, a contribution of different health professionals to patient recovery after solid organ transplantation.

00:12:03: When we talk about transplantation

00:12:05: ,we often

00:12:05: focus on the surgical procedure or on medical treatment but actually the success of transplantation also depends alot what happens afterwards during follow up and long term care.

00:12:18: In this phase, the role of nurses' rehabilitation professional and technical diagnostic staff becomes very important.

00:12:25: This kind of work is particularly relevant in complex and innovative clinical pathways where different professionals need to work together to support their patient recovery.

00:12:37: What interests me is understanding how this professional intervention can really influence a patient outcome For example, not only from a strictly clinical point of view but also in terms of adherence to treatment functional recovery patient education self-management and quality of life.

00:12:57: These are all very important aspects that they often less visible and the less systematically measured compared with traditional biomedical outcome such as graft survival or complication.

00:13:11: For this reason, the main goal of my PSD project is to develop and validate a set outcome indicators that can measure the effectiveness of interdisciplinary non-pharmacological intervention in post transplant care.

00:13:26: The project is structured into three phases over the three years.

00:13:31: at the moment I am working on the first phase which is a scoping review.

00:13:36: This is the first study within the project.

00:13:39: The aim is to map the literature on non-pharmacological intervention, delivered through adult solid organ transplant recipient and identify which outcome indicators are currently used to evaluate this information.

00:13:54: This phase is very important because it gives me theoretical and methodological basis for rest of project.

00:14:02: In the second phase, I plan to work on validation of indicators using a mixed method approach.

00:14:08: This means combining qualitative and quantitative methods for example involving healthcare professionals through focus group instructor evaluation tools.

00:14:18: Then in the third phase, The idea is to test this indicator In a real clinical setting To see whether they are actually useful and applicable in everyday practice And whether They can support quality improvement And in clinical governance in transplant care.

00:14:35: So, overall what I hope to do in this three years is contribute a more integrated and patient-centered model of post transplant care.

00:14:45: In which the role of different health professionals are more clearly recognized as well as effectively measured.

00:14:56: And with that we wrap up today's episode!

00:14:59: Thank you for enjoying us on these journey.

00:15:01: stay tuned for more episodes of Phdbinem behind lab until next time.