Use of stem cells or progenitor cells to treat, delay, prevent, or repair tearing of cruciate ligaments
US US9457051B2 Kathryn Petrucci Animal Cell Therapies, Inc.
Priority 2013-01-22 • Filed 2014-01-22 • Granted 2016-10-04 • Published 2016-10-04
Systems, methods, and apparatuses for securing cell-based products for transport in thermal isolation
US US9738432B1 Kathryn J. Petrucci Animal Cell Therapics, Inc.
Priority 2015-05-29 • Filed 2016-05-09 • Granted 2017-08-22 • Published 2017-08-22
Early Expression of CD34+ vs CD34- Mesenchymal Stem Cells. Inventor: Gene Yeh, et al.
Early and sustained improvements in motor function in rats after infusion of allogeneic umbilical cord-derived mesenchymal stem cells following spinal cord injury - The International Spinal Cord Society - March 2020 - F. M. Moinuddin, Yagiz U. Yolcu, Waseem Wahood, Ahad M. Siddiqui, Bingkun K. Chen, Mohammed Ali Alvi, Anshit Goyal, Jarred J. Nesbitt, Anthony J. Windebank, Jiunn-chern Yeh, Kathy Petrucci & Mohamad Bydon
Early Experience with Allogeneic Umbilical Cord Tissue Derived Mesenchymal Stem Cells in Dogs. ACVS Conference Proceedings. Oct. 2017
Antonio Pozzi, DVM, Diplomate ACVS, Diplomate ECVS Diplomate American College of Veterinary Sports Medicine and Rehabilitation Vetsuisse-University of Zurich; Stan Kim, DVM Diplomate ACVS, University of Florida College of Veterinary Medicine; Kathryn Petrucci, DVM Animal Cell Therapies, Inc.; Gene Yeh PhD, Animal Cell Therapies Inc.
Elbow osteoarthritis is a common cause of forelimb lameness in dogs. The progression of osteoarthritis can lead to lifelong lameness and long-term need for medications such as non-steroidal anti-inflammatories or joint replacement. Osteoarthritis is a complex inflammatory pathway initiated by damage to the joint beginning with the articular cartilage but including all the joint structures including subchondral bone. This inflammatory pathway results in an imbalance of homeostasis leading to an increase in degradative enzymes of the joint such as aggrecanases and matrix metalloproteinases through cytokines such as interleukin-1 beta, tumor necrosis factor alpha, and prostaglandin E2 and an increase in inflammatory cells. This process ultimately leads to a self-perpetuating imbalance in chondrocyte turnover leading to continued worsening of osteoarthritic changes. Decreasing the inflammation associated with osteoarthritis is the goal of medical treatment.
Mesenchymal stem cells are multi-potent cells that have the ability to differentiate into a variety of cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Mesenchymal stem cells are plastic adherent and have spindle fibroblast like morphology in culture, express several surface markers such as CD90, CD44, CD73, and CD105 and lack expression of CD34, CD45, CD14, CD19, and HLA-DR. These cells are thought to be clinically relevant due their immune modulatory capabilities, differentiation capacity and secretion of trophic factors. Since umbilical cord derived mesenchymal stem cells do not express MHC-II, they can be used without requiring immune suppression or matching of donor-recipient.
Current commercial options for veterinary use of mesenchymal stem cells have been centered on the use of autologous adipose derived stromal vascular fraction which is a heterogeneous population of several cell types of varying degrees of maturity. Adipose derived stem cells in stromal vascular fraction represent 1-10% of cell mixture depending upon processing methods. Other major sources of adult mesenchymal stem cells include bone marrow and umbilical cord tissue and cord blood. Potency and proliferation rates of bone marrow or adipose derived stem cells may be affected by age or health status of the donor. On the other hand, umbilical cords are always collected from donors of the same age, thus reducing donor variability. Umbilical cords are easy to collect, do not pose any ethical considerations and do not require additional surgical procedures.
To date, clinical results in veterinary medicine have been largely anecdotal and further research is needed to determine both clinical effect and mechanism of action. The goal of our study was to evaluate the clinical effect of allogeneic umbilical tissue derived mesenchymal stem cells given intra-articularly for the treatment of chronic osteoarthritis. ). Canine umbilical cord tissue stem cells were provided by Animal Cell Therapies, Inc.
(ACT) in San Diego, CA. Umbilical cords were collected from full term puppies via elected C-sections after consent, vaccine and health history was obtained. Cord tissue derived mesenchymal stem cells were characterized by ACT based on standard tri-lineage differentiation, surface cell marker expression, growth and doubling curves, proteomic and gene expression profiles. Cells were also tested for various safety parameters including canine pathogens, general sterility, mycoplasma and endotoxin.
The study design is a prospective, randomized, double blind placebo controlled clinical trial. Patients in the treatment group received mesenchymal stem cells given intra-articularly and the placebo group patients received saline injected intra-articularly. Each patient is followed for 6 months at baseline, one month, three month and six month time points. At each time point, patients are assessed with both objective and subjective measurements including gait analysis, video recording of gait, and measurements of physical parameters with orthopedic examination by a board certified surgeon, arthrocentesis and client questionnaires which included the Client Brief Pain Inventory (CBPI) and the Client Movement Assessment using a Visual Analog Scale (VAS).
The study is ongoing and final results have not been released. However, preliminary results show evidence that there are trends in improvement in force plate parameters of peak vertical force and symmetry as well as client assessments in the CBPI and VAS scores, suggesting that umbilical cord derived allogeneic mesenchymal stem cells may be a valuable treatment option for dogs with osteoarthritis.
Umbilical Cord Stem Cells Improve Motor Function in Rats. American Spinal Cord Injury Conference. April 2019.
Title: Allogeneic umbilical cord derived mesenchymal stem cells transplantation improves motor function in spinal cord injured rats.
Authors: F M Moinuddin, MBBS, PhD1,2; Kathy Petrucci, DVM3; Gene Yeh3; Ahad Siddiqui, PhD4; Anshit Goyal, M.B.B.S.1,2; Yagiz Yolcu, MD1,2; Waseem Wahood, MS1,2; Mohammed Ali Alvi, MBBS1,2; Sandy Goncalves, MS1,2; Nicolas Madigan, M.B., B.Ch., B.A.O., Ph.D.3; Anthony J. Windebank, MD, FAAN3; Mohamad Bydon, MD1,2
1. Mayo Clinic Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA.
2. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
3. Animal Cell Therapies, Inc., San Diego, CA, USA.
4. Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Mohamad Bydon, M.D.
Department of Neurologic Surgery, Mayo Clinic
200 First street SW, Rochester, Minnesota, USA
Objective: Spinal cord injury (SCI) is one of the most devastating forms of trauma resulting in severe functional loss. The injury induces a cascade of secondary insults that limits spontaneous neural tissue regeneration. In recent years, stem cell treatment for SCI has been extensively investigated. Human umbilical cord derived mesenchymal stem cells (UCMSCs) are easier to isolate and expand, and exhibit greater proliferative activity. Using allogeneic UCMSC in spinal cord injured rats could be an appropriate preclinical representation of functional improvement.
Design/Methods: Eight female Sprague-Dawley rats were randomly divided into two groups: control group, and rat UCMSC group. Both groups were subjected to T9 moderate spinal cord contusion injury using a Horizon Impactor machine with 150 kilodynes force. The control group received ringer lactate (RL) injections, whereas the UCMSC group were infused with cells through tail vein 7days after SCI. All rats were examined for motor function by Basso, Beattie, and Bresnahan (BBB) open field locomotion score. The contents of axonal regeneration, cavity volume and glial scar were also explored by immunohistochemistry.
Results: Recovery of hind-limb locomotor function was significantly enhanced in the UCMSC infused animals from 1st week to 13th week after injection. BBB scores in UCMSCs- infused animals were 12.3, 13.7, and 14.1 at 1, 6, and 14 weeks after infusion, respectively, which were significantly higher than those of the RL-infused group (8.1, 9.1, and 10.0). Histologically, the cavity volume was smaller in the UCMSCs treated rats compared to the control group.
Conclusion: Treatment with allogeneic UCMSC can facilitate functional recovery after blunt SCI. UCMSCs may prove to be a useful translational therapeutic strategy that could improve the functional capacity among patients with SCI.
The Sabes Foundation
- Regenerative therapies have been extensively used recently for treatment of SCI, with the objective to improve functional capacity.
- USMSCs may provide a useful option in facilitating functional improvement.
1. Hu SL, Luo HS, Li JT, et al. Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells. Critical care medicine. 2010; 38(11):2181-2189.
2. Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem cells (Dayton, Ohio). 2008; 26(8):2173-2182.
3. Park SI, Lim JY, Jeong CH, et al. Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis. Journal of biomedicine & biotechnology. 2012; 2012:362473.
Intra-Articular Umbilical Cord Derived Mesenchymal Stem Cell Therapy for Chronic Elbow Osteoarthritis in Dogs: A Double-Blinded, Placebo-Controlled Clinical Trial. Frontiers Vet. Sci., 20 December 2019
Freezing and Thawing Techniques
Tissue and Cell Transport Conditions