Cedars-sinai Medical Center

University of California

Emulate, Inc.

Gadi Pelled

Dan Gazit

Zulma Gazit

Dmitriy Sheyn

Hyun W Bae

Debiao Li

Wafa Tawackoli

Christopher David Hinojosa

Geraldine A Hamilton

Norman Wen

Edward M Schwarz

Douglas N Stephens

Katherine W Ferrara

Zhengwei Zhou

Qi Liu

Thomas Michael Kremen

Tendon and ligament injuries are common in orthopaedic clinical practice and cause substantial morbidity in sports and in routine daily activities. While surgical reconstruction is effective, the majority of patients suffer from a prolonged period of recovery because of limited regeneration capacity of the tendon-bone interface. Here, the Inventors have established an approach for promoting tendon/ligament integration. By first recruiting endogenous stem cells to the site of injury, bone morphogenic proteins (BMPs), are then delivered in vivo to promote repair. Significant acceleration of healing via the above methods and compositions leads to fast recovery and return to normal activities, thereby providing new therapeutic avenues for treatment of injuries involving the tendon-bone interface.

Method of endogenous stem cell activation for tendon/ligament osseointegration

Microfluidic 'organ-on-a-chip' devices have been developed with the aim to replicate human tissues in vitro. However, there is no option to quantitatively monitor biological processes that take place within the chip, over time. Destructive methods in order to analyze, tissue formation, gene expression, protein secretion etc. require the harvest of the “tissue” at a certain time point. Described herein are methods and compositions for non-destructive molecular imaging methods and systems in order to quantitatively monitor specific biological processes, over time, within the chip, without the need to harvest.

Method of osteogenic differentiation in microfluidic tissue culture systems

Described herein are compositions and methods related to derivation of human notochordal cells differentiated from induced pluripotent stem cells (iPSCs). The inventors have developed a two-step process for generating these iPSC-derived notochordal cells (iNCs), which can provide a renewable source of therapeutic material for use in degenerative disc disease (DDD). As iNCs are capable of reversing DDD and supporting regeneration of intervertebral disc (IVD) tissue based on the understanding that NC cells maintain homeostasis and repair of other IVD cell types such as nuclear pulposus (NP).

Method for regenerating the interverterbral disc with notochordal cells

In various embodiments, the invention teaches systems and methods for magnetic resonance imaging. In some embodiments, the invention teaches systems and methods for determining the source of pain in intervertebral discs by measuring one or more physiological biomarkers associated with disc pain and/or disc degeneration.

Non-invasive pH-dependent imaging using quantitative chemical exchange saturation transfer (qCEST)

An ultrasound transmitter device for treating a patient is provided. The ultrasound transmitter device includes an imaging probe; an imaging array; and a therapeutic ultrasound device, wherein the imaging probe is configured to guide the therapeutic ultrasound device to the patients treatment site by use of ultrasound imaging with the imaging array, wherein the therapeutic ultrasound device is configured to produce a controlled intensity of ultrasound energy for treating the patients treatment site, and wherein the imaging probe and the therapeutic ultrasound device are configured to work in conjunction with one another to apply therapeutic ultrasound to tissue or bone graft sites in the patient.

Transfection and drug delivery

Described herein are methods and compositions using PTH and mesenchymal stem cells (MSCs) for treatment of osteoporosis, bone fractures, and related conditions. Administration of both PTH and MSCs leads to increased homing of MSCs to sites of vertebral bone and rib fracture. The described methods and compositions provide therapeutic approaches that rely, in-part, on stem cell capacity for regeneration and repair. The potential for enhanced bone formation and fracture repair may allow for both preventative and palliative treatments in osteoporotic patients, with combined PTH+MSC therapy producing bone regeneration capacity that is significantly superior to either treatment alone.

Method for non surgical repair of vertebral compression fractures

The present invention teaches novel methods of diagnosing and prognosing conditions associated with tissue degeneration and/or pain, including intervertebral disc degeneration, discogenic pain, osteoarthritis, rheumatoid arthritis, and articular cartilage injury. Using the inventive noninvasive imaging methods, the diagnosis and prognosis of back pain and related conditions can be quickly and accurately determined by detecting one or more biomarkers disclosed herein.

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Los Angeles, CA, United States of America

Gadi Pelled