Graziella Pellegrini | |
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![]() Pellegrini speaks on regenerative medicine at the 2015 World Economic Forum. | |
Born | July 12, 1961 |
Alma mater | University of Genoa |
Known for | Regenerative medicine |
Awards | Louis-Jeantet Prize for Medicine (2020) |
Scientific career | |
Institutions | University of Modena and Reggio Emilia |
Graziella Pellegrini (born July 12, 1961) is an Italian Professor of Cell Biology and the Cell Therapy Program Coordinator at the University of Modena and Reggio Emilia. She has developed and championed cell therapy protocols in hospitals across Italy.
Pellegrini was born in Genoa. [1] She studied molecular pharmacology at the University of Genoa, where she earned her PhD in 1988. [1] She continued to study chemistry and pharmacology at the University of Genoa, and completed two subsequent degrees in 1989. [1] [2] Pellegrini completed extra training to become a pharmacist. [1]
Pellegrini was appointed to the Italian National Institute for Cancer Research in 1988. She held positions at Celllife Biotechnology, the Advanced Biotechnology Center and the Veneto Eye Bank Association. [3] She is best known for her work in translational medicine, and has developed epithelial stem cell mediated cell and gene therapies. [4] [5] [6] She has worked with Michele de Luca for most of her academic career. In 1990 Pellegrini established the first urethral stem cell cultures for humans, which could be used to regenerate the urethra in patients with posterior hypospadias. [7]
She showed that the p63 transcription factor, a homologue of P53 that is essential for regenerative proliferation in the development of epithelial cells, can distinguish human keratinocyte cells from their transient amplifying keratinocyte analogues. [8] The identification of this marker is important in the clinical application of epithelial cultures for cell therapy. [8]
In 2006 Pellegrini was appointed as an associate professor at the University of Modena and Reggio Emilia. She leads the Center for Regenerative Medicine “Stefano Ferrari”. Pellegrini has used the epithelial stem cells for the treatment of skin disease. She first outlined the feasibility of ex vivo gene therapy of laminin-332 junctional epidermolysis bullosa in 2006. [9] This involved transplanting autologous epidermis flaps from epidermal stem cells that had been genetically corrected. [9] [10] She demonstrated the first successful clinical trial to treat junctional epidermolysis bullosa. [11] For the following two years, Pellegrini and De Luca observed initial stem cell patients, when it became obvious that they could scale the technology. [3] In 2017 the epithelial stem cells were used to treat a seven-year-old boy who had lost 80% of his skin to junctional epidermolysis bullosa. [12]
In 2008 Pellegrini and De Luca co-founded the Holostem Terapie Avanzate, a biotechnology spin-out that develops advanced therapy producets that use epithelial stem cell cultures. [13] They developed a culture system that creates limbal stem cell for the regeneration of corneas, which can restore vision to patients ocular burns who are deemed incurable. [14] [15] This system, Holoclar, was recognised by the European Medicines Agency in 2008, and received its approval for marketing from the European Commission in 2015. [3] [16] [17] Holoclar is the first stem cell based medicinal product to be approved by the European Commission. [18]
In 2020 Graziella Pellegrini and Michele De Luca, shared the Louis-Jeantet Prize for Medicine for the development of epithelial stem cell-based regenerative therapy in patients with severe eye and skin disease. [19]
Pellegrini provides expert opinion for the World Economic Forum. [5] [20]
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. The cornea can be reshaped by surgical procedures such as LASIK.
Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations.
Type II keratins constitutes the Type II intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. The type 2 cytokeratins consist of basic or neutral, high molecular weight proteins which in vivo are arranged in pairs of heterotypic Type I and Type II keratin chains, coexpressed during differentiation of simple and stratified epithelial tissues. It has been seen that Type II Keratins are developed before Type 1 keratins during human embryonic development.
Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.
Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion.
Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.
Elaine V. Fuchs is an American cell biologist famous for her work on the biology and molecular mechanisms of mammalian skin and skin diseases, who helped lead the modernization of dermatology. Fuchs pioneered reverse genetics approaches, which assess protein function first and then assess its role in development and disease. In particular, Fuchs researches skin stem cells and their production of hair and skin. She is an investigator at the Howard Hughes Medical Institute and the Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development at The Rockefeller University.
Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.
Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.
Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an inherited disease affecting the skin and other organs.
Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.
Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.
Anchoring fibrils extend from the basal lamina of epithelial cells and attach to the lamina reticularis by wrapping around the reticular fiber bundles. The basal lamina and lamina reticularis together make up the basement membrane. Anchoring fibrils are essential to the functional integrity of the dermoepidermal junction.
Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.
A limbal ring is a dark ring around the iris of the eye, where the sclera meets the cornea. It is a dark-colored manifestation of the corneal limbus resulting from optical properties of the region. The appearance and visibility of the limbal ring can be negatively affected by a variety of medical conditions concerning the peripheral cornea. It has been suggested that limbal ring thickness may correlate with health or youthfulness and may contribute to facial attractiveness. The thickness of the limbal ring varies by pupil dilation - when the pupil is larger, the limbal ring narrows. Some contact lenses are colored to simulate limbal rings.
Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles, dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers. Furthermore, these dermal fibroblasts produce the protein molecules including laminin and fibronectin which comprise the extracellular matrix. By creating the extracellular matrix between the dermis and epidermis, fibroblasts allow the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin.
A Muse cell is an endogenous non-cancerous pluripotent stem cell. They reside in the connective tissue of nearly every organ including the umbilical cord, bone marrow and peripheral blood. They are collectable from commercially obtainable mesenchymal cells such as human fibroblasts, bone marrow-mesenchymal stem cells and adipose-derived stem cells. Muse cells are able to generate cells representative of all three germ layers from a single cell both spontaneously and under cytokine induction. Expression of pluripotency genes and triploblastic differentiation are self-renewable over generations. Muse cells do not undergo teratoma formation when transplanted into a host environment in vivo. This can be explained in part by their intrinsically low telomerase activity, eradicating the risk of tumorigenesis through unbridled cell proliferation. They were discovered in 2010 by Mari Dezawa and her research group. Clinical trials for acute myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, amyotrophic lateral sclerosis, acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection, are conducted by Life Science Institute, Inc., a group company of Mitsubishi Chemical Holdings company. In february 2023, however, Mitsubishi Chemical Group decided to discontinue the development of a regenerative medicine product (CL2020) using Muse Cells. Physician-led clinical trial for neonatal hypoxic-ischemic encephalopathy was also started. The summary results of a randomized double-blind placebo-controlled clinical trial in patients with stroke was announced.
Cord lining, cord tissue, or umbilical cord lining membrane, is the outermost layer of the umbilical cord. As the umbilical cord itself is an extension of the placenta, the umbilical cord lining membrane is an extension of the amniotic membrane covering the placenta. The umbilical cord lining membrane comprises two layers: the amniotic layer and the sub-amniotic layer. The umbilical cord lining membrane is a rich source of two strains of stem cells (CLSCs): epithelial stem cells (CLECs) and mesenchymal stem cells (CLMCs). Discovered by Singapore-based CellResearch Corporation in 2004, this is the best known source for harvesting human stem cells.
Limbal stem cells, also known as corneal epithelial stem cells, are unipotent stem cells located in the basal epithelial layer of the corneal limbus. They form the border between the cornea and the sclera. Characteristics of limbal stem cells include a slow turnover rate, high proliferative potential, clonogenicity, expression of stem cell markers, as well as the ability to regenerate the entire corneal epithelium. Limbal stem cell proliferation has the role of maintaining the cornea; for example, by replacing cells that are lost via tears. Additionally, these cells also prevent the conjunctival epithelial cells from migrating onto the surface of the cornea.
Valerie Horsley is an American cell and developmental biologist. She currently works as an associate professor at Yale University, where she has extensively researched the growth, restoration, and maintenance of skin cells. She is a currently a member of the Yale Cancer Center and Yale Stem Cell Center. She received a Presidential Early Career Award for Scientists and Engineers in 2012 and in 2013 she was the recipient of the Rosalind Franklin Young Investigator Award.