title: Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model.
abstract: The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5×10(7) cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future.
  
  
  CONCLUSIONS
  To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These experimental results are currently in preparation for publication.) Before applying the cartilage regeneration technique in a human clinical trial, it seemed necessary to confirm the consistent result in a larger animal model. At 12 weeks postoperatively, the minipigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. This evidence of consistent cartilage regeneration with composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future.
authors.affiliation: Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Ajou University Hospital, Ajou University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju-do, Republic of Korea.
authors.forename: Chul-Won
authors.initials: CW
authors.lastname: Ha
authors.affiliation: Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Ajou University Hospital, Ajou University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju-do, Republic of Korea whybe1122@gmail.com.
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
authors.affiliation: Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Ajou University Hospital, Ajou University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju-do, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Ajou University Hospital, Ajou University School of Medicine, Seoul, Republic of Korea; Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju-do, Republic of Korea.
authors.forename: Yong-Geun
authors.initials: YG
authors.lastname: Park
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000293:injuries; D002356:Cartilage / Q000187:drug effects / Q000293:injuries*; D002454:Cell Differentiation; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D020219:Chondrogenesis / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D013640:Tarsal Joints / Q000187:drug effects / Q000293:injuries; D023822:Tissue Engineering / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: Cartilage; Human umbilical cord blood; Hyaluronic acid; Mesenchymal stem cell; Regeneration