Cell Seeding Densities in Autologous Chondrocyte Implantation Techniques for Cartilage Repair

Abstract

Cartilage repair techniques have been among the most intensively investigated treatments in orthopedics for the past decade, and several different treatment modalities are currently available. Despite the extensive research effort within this field, the generation of hyaline cartilage remains a considerable challenge. There are many parameters attendant to each of the cartilage repair techniques that can affect the amount and types of reparative tissue generated in the cartilage defect, and some of the most fundamental of these parameters have yet to be fully investigated. For procedures in which in vitro–cultured autologous chondrocytes are implanted under a periosteal or synthetic membrane cover, or seeded onto a porous membrane or scaffold, little is known about how the number of cells affects the clinical outcome. Few published clinical studies address the cell seeding density that was employed. The principal objective of this review is to provide an overview of the cell seeding densities used in cell-based treatments currently available in the clinic for cartilage repair. Select preclinical studies that have informed the use of specific cell seeding densities in the clinic are also discussed.

Optimal Seeding Densities for In Vitro Chondrogenesis of Two- and Three-Dimensional-Isolated and -Expanded Bone Marrow-Derived Mesenchymal Stromal Stem Cells Within a Porous Collagen Scaffold

“…Constructs containing 50 × 10 6 BMSCs/cm 3 at the time of seeding displayed stunted chondrogenesis in comparison to 10 and 5 × 10 6 BMSCs/cm 3 , which could relate to cell crowding, nutrient limitation, and relatively less volume available for ECM deposition. 45,46 These findings suggest that the optimal seeding density for chondrogenesis of 2D-expanded BMSCs within collagen scaffolds is 5-10 × 10 6 BMSCs/ cm 3 .…”

Effects of insulin-like growth factor 1 and basic fibroblast growth factor on the morphology and proliferation of chondrocytes embedded in Matrigel in a microfluidic platform

“…Subsequently, the chondrocytes that have been expanded and harvested in vitro are directly transplanted back into the defector utilized to engineer implantable grafts (10). However, the use of ACI treatment is limited due to the inevitable dedifferentiation of seeded cells that happens during the in vitro expansion (11).…”

Efficacy and Safety of Autologous Cell Therapies for Knee Cartilage Defects (Autologous Stem Cells, Chondrocytes or the Two): Randomized Controlled Trial Design

“…In addition, the third arm, which combines in vitro culture expanded autologous chondrocytes and BM-MSCs, represents a firstin-man clinical intervention using a combination of these cell populations for the treatment of cartilage injury (the second research hypothesis). Furthermore, we have purposefully proposed a wide range of number of cells (i.e., doses) due to the fact that although a wide range of cell numbers are used in ACI and equivalent procedures, there is no clear scientific evidence for the optimal dose [50]. Hence, we included a range covering both that examined in the reviewed literature (0.5 to >10 million cells/cm 2 of defect area) [50] and the maximum range used in our center, hoping that the results from this trial could give an indication as to whether more or less cells produced a better clinical outcome or quality of repair tissue.…”