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Vascular endothelial transdifferentiation to mesenchymal stem-like cells



Technology:
Method to transdifferentiate vascular endothelial cells to MSC-like cells

Markets Addressed


The immuno-suppressive capacity and regenerative potential of MSCs have generated clinical interest for their use in a variety of fields, including:

Immuno-suppression
• Stem cell transplantation/Hematological malignancies - prevention of graft-versus-host disease; facilitation of tissue repair

Tissue engineering and regeneration
• Crohn’s disease - Repair of fistulas
• Myocardial infarction – Regeneration of cardiac tissue
• Orthopedic surgery – Repair of bone, cartilage, tendon, and other connective tissues for the repair of bone fractures, cartilage injury, and meniscus tears.
• Bone disease – Bone regeneration for osteoarthritis and osteogenesis imperfecta.

Innovations and Advantages


Mesenchymal stem cells (MSC) can give rise to various cell types, including chondrocytes (collagen producing cells found in cartilage), osteoblasts (bone producing cells) and adipocytes (fat cells). MSCs secrete a broad spectrum of bioactive molecules, including trophic factors, anti-apoptotic molecules, angiogenic factors and immunomodulators, which help create regenerative microenvironments localized to sites of tissue injury. Therefore, MSCs may be an important therapeutic tool for the replacement or repair of damaged tissues such as bone, cartilage, or tendon. The most common source of MSCs is the bone marrow, however, aspirating bone marrow from patients is an invasive, low-yield procedure. In addition, the number and differentiating potential of bone marrow MSCs decreases with age. Therefore, the search for alternative sources of MSCs is of significant value.

Researchers in Dr. Olsen’s laboratory developed a novel method by which mature vascular endothelial cells can be induced to trans-differentiate into MSC-like cells. Since vascular endothelial cells can easily be obtained in large numbers (for example, from umbilical cord blood), these methods have a significant advantage over isolating MSCs from bone marrow.

The lab demonstrated that treatment of vascular endothelial cells with certain factors activates a receptor which decreases the expression of endothelial markers such as VE-cadherin. Furthermore, the induced MSC-like cells demonstrate multipotency. When cultured in lineage specific culture medium, the endothelial derived cells express lineage-specific transcription factors and target genes for chondrocytes, osteoblasts or adipocytes.

Additional Information


Intellectual Property Status: Patent(s) pending





Inventor(s):
    Medici, Damian
    Olsen, Bjorn R.

Categories:
For further information, please contact:
Grant Zimmermann, Director of Business Development
(617) 495-3067
Reference Harvard Case #3602