Bioengineering of human adipose tissue and cell-based therapy of obesity
- Micro-physio/pathological models of adipose tissue (MPM)
- Tissue-based therapy of obesity associated metabolic diseases
- Human adipose tissue physiology (WAT/BAT)
Obesity is a global pandemic with a high prevalence responsible for about 3 million annual deaths, and with associated high-impact morbidities, such as type 2 diabetes and non-alcoholic steatohepatitis (NASH). Despite new drugs in clinical phases and the increase in the use of bariatric surgery, about 20% of patients treated with drugs are resistant to treatments and in total therapeutic failure. Today, no drugs against NASH are available. Development of alternative therapies against obesity is urgent.
More than a decade of scientific research conducted on animal models, shows that transplantation of beige adipose tissue (BAT) in obese mice allows a multiple therapy action, that acts at the level of weight gain, type 2 diabetes and fatty liver. Therefore, BAT transplantation is a very promising therapeutic avenue that nevertheless clashes with (1) the absence of an abundant and clinically relevant source of BAT in humans, and (2) the technological lock of maintaining human adipose tissue in culture, that is required for the conversion of white adipose tissue into beige adipose tissue.
Our scientific questions are designed:
1/ To propose innovative 3D in vitro models of human adipose tissue to investigate cellular and molecular mechanisms involved in physiology and pathology of adipose tissue
2/ To develop ExAdEx proprietary technology for clinical applications of BAT transplantation
Fig 1 - Beiging potential. The ExAdEx products were maintained in vitro for 30 days and then were induced to undergo beiging. After two weeks, UCP1 was revealed by immunofluorescence. Top image: Native human white adipose tissue. Bottom image: ExAdEx-BAT, human beige cell therapy product. Blue; Nuclei, Red (Adipocytes), Green (Beige adipocytes expressing UCP1).
ExAdEx-Innov is leading preclinical studies of a patented technology originated from academic research centers based at the University Côte d’Azur (the "Stem Cells and Differentiation" team at the iBV, in collaboration with the Nice CHU and the Cell and Gene Therapy Unit).
ExAdEx technology is an innovative process for culturing human adipose tissues in 3D that opens the way for the first tissue-based therapeutic solution for metabolic diseases associated with obesity. This technology is protected by 2 international patents (UCA and CHU are co-inventors) and a unique know-how resulting from more than 30 years of experience in the field of obesity and stem cells.
With the support of the Young Entrepreneur Program of the Labex Signalife, the academic team has also developed the first RD platform of human adipose tissue, allowing the realization of pre-clinical tests on physiological and pathological models. The models from this platform are currently marketed by ExAdEx-Innov in the cosmetics sector and are the subject of a commercial collaboration with the CRO DIVA-Expertise (Toulouse), leader on the national market.
ExAdEx-Innov is currently preparing a fundraising event with private investors to accelerate its pre-clinical development, with the support of the PACA-Est incubator and the Métropôle Nice Côte d’Azur-Eurobiomed HealthTech accelerator.
Fig 2 - ExAdEx process for clinical purpose. Following liposuccion, adipose tissue is process in 4 weeks to induce first adipose progenitors amplification in 3D culture in defined cell culture medium, then process for beiging induction to obtain the ExAdEx-BAT injectable cell therapy product
First in class in vitro micro-physiological model of human adipose tissue
ExAdEx-Innov develops, in collaboration with the “Stem cells and différentiation” teams at iBV, 3D physiological models of human adipose tissue that allows:
- Functional studies of physiological and pathological processes of human adipose tissue biology
- Commercial models for the cosmetic industry
Preclinical study for BAT transplantation
ExAdEx-Innov engages its therapeutic development with historical academic partners and via new collaborations with the RESTORE Institute in Toulouse, via a CNRS prematuration program, and the Digestive Surgery Department of CHU Nice as part of an exploratory clinical trial.
Vincent DANI, PhD (CEO et Co-Founder) has 10 years of experience in bioengineering and a dual competence in clinical research and Deeptech entrepreneurship.He is the main inventor of the ExAdEx technology
Luigi FORMICOLA, PhD, MBA (COO et Co-Founder) has 10 years of experience in biotech startup and pharmaceutical project management
Christian DANI, PhD, (Scientific Advisor) Director of the "Stem Cells and Differentiation" team, academic partner of the company
Alain DOGLIO, PhD, (Scientific Advisor) Director of the Cell and Gene Therapy Unit at Nice University Hospital
Bérengère CHIGNON-SICARD, MD, PhD, (Scientific Advisor) surgeon specialized in adipose tissue grafts and ANSM expert
Cynthia LE MOUROUX, Apprenti CDD , Licence Professionnelle Bio-Industries et Biotechnologies (UCA)
- Patent 1 : “Method for in vitro or ex vitro amplification of human adipose tissue stem cells“. Number : FR1900287. PCT/EP2020/050720
- Patent 2: “Method for amplifying brown or beige adipocyte stem cells“. Number: FR2007407 2020. PCT/EP2021/069888
- Yao X, Dani V, Dani C. Human. “Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation”. Front Endocrinol (Lausanne). 2020 Jan 21;10:932. https://www.frontiersin.org/articles/10.3389/fendo.2019.00932/full
- Dani, V., Yao, X. & Dani, C. “Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives”. Rev Endocr Metab Disord (2021). https://doi.org/10.1007/s11154-021-09632-6
- Xi Yao, Vincent Dani, Christian Dani. “Developmental origins of adipocytes: What we learn from human pluripotent stem cells”. Scientific Principles of Adipose Stem Cells, Academic Press, (2022), Pages 11-21, ISBN 9780128193761. https://doi.org/10.1016/B978-0-12-819376-1.00015-9
- Vincent Dani, Solène Bruni-Favier, Bérengère Chignon-Sicard, Agnès Loubat, Alain Doglio, and Christian Dani. “ExAdEx: A simple method to maintain human adipose tissue in long-term cultures reveals differential expansion of adipose progenitor cell subpopulations in fibrotic and pro-inflammatory microenvironments”. Research Square (Preprint 2022). https://www.researchsquare.com/article/rs-1733405/v2
- Vincent Dani, Solène Bruni-Favier, Bérengère Chignon-Sicard, Agnès Loubat, Alain Doglio, and Christian Dani. “Regulation of adipose progenitor cell expansion in a novel micro-physiological model of human adipose tissue mimicking fibrotic and pro-inflammatory microenvironments”. Cells (2022), 11(18), 2798. https://doi.org/10.3390/cells11182798
- Vincent Dani, Xi Yao, Solène Bruni-Favier, Christian Dani. “Embryonic origins of the three types of adipocytes and novel in vitro models for studying development of human adipocytes”. Médecine des Maladies Métaboliques (2022) In press, Corrected proofs. https://doi.org/10.1016/j.mmm.2022.09.009
2022 - Innovative Company Award - Métropole Nice Côte d'Azur
2022 - Laureate of the Labex SignaLife Young Entrepreneur Program
2022 - Laureate of the Innovative Center for Entrepreneurship (ICE) Prize
2022 - Laureate of the CNRS-Innovation Prematuration Program
2022 - Laureate of a Nice University Hospital “Call for Internal Project“
2022 - I-Lab Nomination
2022 - HealthTech Eurobiomed Accelerator, 2nd promotion
2022 - BPIfrance DeepTech Certification
2021 - RISE CNRS Innovation Program 4th Promotion
2021 - Incubated at the PACA-Est Incubator
iBV is very proud to announce the launch of ExAdEx-Innov, a new start-up led by Vincent DANI, post-doc at iBV since 2019
iBV - Institut de Biologie Valrose
Université Nice Sophia Antipolis
Faculté de médecine
28 Avenue de Valombrose
06189 Nice cedex 2