Bone Marrow Stromal Cells in a Liquid Fibrin Matrix Improve the Healing Process of Patellar Tendon Window Defects

Abstract

Following injury, ligaments and tendons do not regain their normal biological and biomechanical status. This study analyzed whether an injection of human bone marrow stromal cells (BMSC) or human fibroblast in a liquid fibrin matrix influences the histological results, ultrastructural morphology, mRNA expression of essential extracellular matrix proteins, and material properties of the healing tissue. Standardized full-thickness, full-length defects of the central portion of patellar tendons were created in 96 immunodeficient rats, and filled with human BMSC in a fibrin matrix (BMSC group), human fibroblasts in a fibrin matrix (fibroblast group), or fibrin matrix only (matrix group), or left untreated (defect group). Histological sections revealed more mature tissue formation with more regular patterns of cell distribution in the BMSC group, without signs of ectopic tissue formation into bone or cartilage. Mean collagen fibril diameter and relative area covered by collagen fibrils were significantly higher at 10 and 20 days postoperatively in the BMSC group compared to the defect and matrix groups, and comparable to normal tendon tissue. Further, collagen I mRNA expression, collagen I/collagen III mRNA ratio, and Young's modulus were significantly increased at 20 days postoperatively in comparison to the defect and matrix groups. In the fibroblast group, only mean collagen fibril diameter was significantly higher compared to the defect group, whereas the other biological and biomechanical parameters were not significantly improved. This study reveals that an injection of BMSC in a liquid fibrin matrix stimulates histological, ultrastructural, molecular biologic, and biomechanical parameters of patellar tendon healing, whereas injection of fibroblasts in fibrin matrix had only minor effects on the stimulation of tendon healing.

The past, present and future in scaffold-based tendon treatments

“…The ideal carrier system should prevent cell membrane rupture during the injection process; create increased tissue integration through fast in situ self-assembly; facilitate long-term cell survival and functionality maintenance; and allow spatiotemporal release of the cargo [222][223][224][225][226][227][228][229][230][231]. Preclinical data using either collagen [232] or fibrin [233] hydrogels have demonstrated improved mechanical properties, histological scores, tissue integration and restored functionality using TCs and various stem cell populations [234,235], however clinical use of injectable cell/hydrogel systems is still to be realised.…”

Human iPSC-Derived Neural Crest Stem Cells Promote Tendon Repair in a Rat Patellar Tendon Window Defect Model

“…Mesenchymal stem cells (MSCs) are a widely used cell source. [8][9][10][11] These cells have great capacity for differentiating into mesenchymal lineages, including tenocytes. However, MSCs may express alkaline phosphatase activity and form ectopic bone in repaired tendon.…”

Umbilical Cord Perivascular Cells: A Mesenchymal Cell Source for Treatment of Tendon Injuries

“…Prior to the present study, the highest reported values of increase in wound tensile strength following cell administration was that of Hankemeier et al, [28] who created standardized central full-thickness patellar tendon defects in immunodeficient rats, filled them with human BMSC in a fibrin matrix, and showed 51.5% of normal tensile strength 20 days after surgery. This was an improvement over the results of Young et al, [7] who repaired rabbit Achilles tendons using MSCs seeded on a biodegradable scaffold and showed 37.2% of normal tensile strength values, by 12 weeks.…”