Research Overview



Stem cell therapy

Cell-based therapies aim to return damaged or injured tissue to a more normal structure and function. An overarching goal in stem cell therapy is to protect and restore the articular surface, thereby preventing further joint degradation. We are harnessing the chondrogenic differentiation capabilities as well as the immunomodulatory properties of stem cells to address cartilage injury and global joint inflammation the ensues following trauma. By mitigating joint inflammation, we are hoping to prevent inflammation-driven degeneration of the joint.

harvesting bone marrow, Dr. Kyla Ortved, New Bolton Center

Bone marrow is harvested from the sternum of a sedated horse and culture-expanded in the lab. We are using these cells to form cartilage-like pellets through chondrogenic differentiation, in order to optimize a cell-source that could be used to repair cartilage defects in the joint.


Extracellular Vesicles

Extra-cellular vesicles (EV) carry important signaling proteins, lipids and RNA. These membrane bound particles are released by cells, including stem cells, and can be used as a sensitive biomarker of disease and a potential therapeutic. We are investigating EVs in joint fluid of horses with naturally-occurring PTOA and EVs collected from stem cells cultured in different environments.

TEM of EV from horse stem cells
Transmission electron microscopy (TEM) image of an EV derived from
horse stem cells.

Gene Therapy

Gene therapy also has the potential to bolster the weak healing response in articular cartilage and decrease joint inflammation. Dr. Ortved has demonstrated improved cartilage repair in large, full-thickness chondral defects created in the lateral trochlear ridge of the horse femur using autologous chondrocytes transduced ex vivo with an adeno-associated virus (AAV) vector overexpressing the anabolic protein IGF-I. We have also demonstrated the ability of the anti-inflammatory cytokine IL-10 to protect cartilage from degeneration and have shown that IL-10 can be safely overexpressed in vivo following direct injection of AAV-IL-10 into horse joints. We are now beginning to assess the effects of this therapy in vivo to determine if it can mitigate the post- traumatic inflammatory response that occurs following joint injury.

Arthroscopic images of empty (a), implanted (b) and healing defects 8 weeks postimplantation (c-f)
Arthroscopic images of empty (a), implanted (b) and healing defects 8 weeks postimplantation (c-f). (c) Defects repaired with rAAV5-IGF-I transduced chondrocytes had better defect fill and white “cartilage- like” tissue compared to the defects filled with (d) rAAV5-GFP transduced chondrocytes, (e) untransduced chondrocytes, or (f) fibrin alone.

AAV Vectors

Equine chondrocytes transduced with an AAV vector
Horse chondrocytes have been transduced with an AAV vector, expressing red fluorescent protein. .

Dr. Ortved has also demonstrated that AAV vectors can be used to safely transduce equine articular cells in vivo with efficient, sustained expression of a therapeutic transgene. More recently, Dr. Ortved has been investigating AAV-mediated overexpression of interleukin-10 (IL-10), an immunomodulatory cytokine. She showed that L-10 overexpression downregulates expression of proinflammatory mediators in inflamed chondrocytes in vitro. We are now beginning to assess the effects of this therapy in vivo to determine if it can mitigate the post- traumatic inflammatory response that occurs following joint injury.


Post-traumatic Osteoarthritis (PTOA)

We are investigating changes in gene expression in cartilage, synovium, fat pad and meniscus in horses with PTOA, in order to understand how different pathways are affected by trauma. We are also developing an ex vivo model of PTOA to help understand the histologic, microscopic and molecular changes that occur post-traumatically.