Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model

PLoS One. 2016 Nov 8;11(11):e0165446. doi: 10.1371/journal.pone.0165446. eCollection 2016.

Abstract

Background: Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model.

Methods: Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically.

Findings: Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group.

Conclusions: The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / physiology*
  • Fetal Blood / physiology*
  • Humans
  • Hyaluronic Acid / therapeutic use*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / therapeutic use*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / physiology*
  • Rabbits
  • Tissue Engineering / methods
  • Wound Healing / physiology*

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hyaluronic Acid

Grants and funding

This research was supported by a grant (HI14C3484) of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea. The funding sources had no involvement in the study design, collection, data analysis, data interpretation, writing of the manuscript, or the decision to submit the manuscript for publication.