Cultures, Products and Methods Using Stem Cells

Reference Number: 01-04

Inventor: Mark L. Weiss, Deryl L. Troyer, Duane Davis, and Kathy E. Mitchell

Description:

Research at Kansas State University has produced an invention for isolating, storing, and using multipotent mesenchymal stromal cells (MSCs) derived from the Wharton’s jelly of the umbilical cord (referred to as matrix cells). Matrix cells can be collected after umbilical cord blood collection without impacting cord blood collection. Matrix cells serve as an alternative to other MSC sources, including adult bone marrow, adipose-derived MSCs or umbilical cord blood-derived MSCs.

Advantages:

Matrix cells are harvested non-invasively from a species-specific, readily available source that is non-controversial, inexhaustible, inexpensive, substantially free from cord blood and can be cryopreserved for banking. Matrix cells are at least multipotent and may be nearly pluripotent for a variety of end uses. Below are additional potential advantages of this technology:

  • Application to any amniotic animal, including humans, horses, companion animals, food animals and laboratory animals (potentially any animal with an umbilical cord)
  • Matrix cells are easily expanded and can be rapidly grown in culture
  • Largest population of stem cells yet identified (distinct from stem cells found in umbilical cord blood)
  • Matrix cells express genes from all three embryonic germ layers - endoderm, mesoderm, and ectoderm
  • Matrix cells grow more rapidly and longer in culture than adult bone marrow MSCs and have a higher initial colony forming unit-fibroblast (CFU-F) frequency {CFU-F is the best in vitro marker of stemmy MSCs}, and have a significant population of ganglioside GD2 positive cells, which has recently reported to be a marker for primitive mesenchymal stem cells
  • Allogeneic transplantation, transplantation across HLA/MHC classification, may be possible
  • Matrix cells have been shown to be non-tumorigenic in animal models tested to date, and therefore have fewer concerns compared to other multipotent and pluripotent stem cell lines
Applications:

This invention provides a source of stem cells for research and therapeutic uses. Based on the data to date, the following are some potential uses of these cells:

Therapeutic:
  • Matrix cells home to tumors and can be used as delivery vehicles for genes or pro-drugs
  • Possible treatment for stroke, neurodegenerative diseases, diabetes, vascular conditions and inflammation
  • Treatment of Graft vs Host Disease (GVHD), as a substitute for bone marrow derived mesenchymal stromal cells
Media, Collection and Storage of Cells:
  • As feeder cells for establishment and/or growing other stem cells
  • Collection and Banking to augment the value of umbilical cord blood banking
Tissue Engineering and Transplantation:
  • Wound healing, bone or cartilage defect repair
  • Blood vessel and heart valve tissue engineering & replacement
  • Orthopedic applications, including joints and tendons for human, horses and other companion animals
  • Induction of immune tolerance to enable solid organ transplantation
  • Co-graft with autologous UC blood to enable cord blood stem cell engraftment
Patent Status
  • U.S. Patent 7,736,892 issued on June 15, 2010
  • U.S. Patent 8,268,302 issued on September 18, 2012
Related Publications:
  • Mitchell K, Weiss M et al. Matrix Cells from Wharton’s Jelly From Neurons and Glia. Stem Cells 2003; 21: 50-60.
  • Weiss M, Mitchell K et al. Transplantation of Porcine Umbilical Cord Matrix Cells Into the Rat Brain. Experimental Neurology 2003; 182: 288-299.
  • Medicetty S, Bledsoe A et al. Transplantation of Pig Stem Cells Into Rat Brain: Proliferation During the First 8 Weeks. Experimental Neurology 2004; 190: 32-41.
  • Weiss M, Medicetty S et al. Human Umbilical Cord Matrix Stem Cells: Preliminary Characterization and Effect of Transplantation in a Rodent Model of Parkinson’s Disease. Stem Cells 2006; 24: 781-792.
  • Carlin R, Davis D et al. Expression of Early Transcription Factors Oct-4, Sox-2 and Nanog by Procine Umbilical Cord (PUC) Matrix Cells. Reproductive Biology and Endocrinology 2006; 4: 8.
  • Weiss M, Troyer D et al. Stem Cells in the Umbilical Cord. Stem Cell Reviews 2006; 2: 155-162.
  • Rachakatla R, Marini F et al. Development of Human Umbilical Cord Matrix Stem Cell-Based Gene Therapy for Experimental Lung Tumors. Cancer Gene Therapy 2007; 14: 828-835.
  • Troyer D, Weiss M. Concise Review: Wharton’s Jelly-derived Cells are a Primitive Stromal Cell Population. Stem Cells 2007; 26: 591-599.
  • Seshareddy K, Troyer D et al. Method to Isolate Mesenchymal-Like Cells from Wharton’s Jelly of Umbilical Cord. Methods in Cell Biology 2008; 86: 101-119.
  • Weiss M, Anderson C et al. Immune Properties of Human Umbilical Cord Wharton’s Jelly-Derived Cells. Stem Cells 2008; 26: 2895-2874
  • Ayuzawa R, Doi C et al. Naïve Human Umbilical Cord Matrix Derived Stem Cells Significantly Attenuate Growth of Human Breast Cancer Cells In Vitro and In Vivo. Cancer Letters 2009; 280: 31-37.
  • Ganta C, Chiyo D et al. Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post-Tumor Cell Inoculation. Cancer Res 2009; 69: 1815-1820.
  • He H, McHaney M et al. Cloning and Characterization of 3.1kb Promoter Region of the Oct4 Gene from the Fischer 344 Rat. The Open Stem Cell Journal 2009; 1:30-39

Kansas State University Research Foundation seeks to have discussions with companies that are interested in licensing and/or research collaborations.

Interested parties should contact:

Kansas State University Institute for Commercialization (KSU-IC)
2005 Research Park Circle Manhattan, KS 66502
Tel: 785-532-3900 Fax: 785-532-3909
E-Mail: ic@k-state.edu