No Correlation Exists Between Tibial- and Femoral-Based Measurements of Patella Alta in a Population With Chronic Patellofemoral Pain or Instability Undergoing Patella Distalization.

PURPOSE: To investigate whether the patellotrochlear index (PTI) predicts patella alta as determined by tibial-based methods of Insall-Salvati (IS) and Caton-Deschamp (CDI) indexes in a pathological population (with patellofemoral pain and/or instability), in addition to determining whether PTI and sagittal patellofemoral engagement (SPE) correlate with trochlea length as determined by lateral condyle index (LCI). METHODS: Patients with confirmed patella alta (IS/CDI ratio >1.2) undergoing tibial tubercle osteotomy for patellofemoral pain/instability with an available magnetic resonance imaging (MRI) scans were included. Patients who had undergone previous soft-tissue realignment, previous surgery, or trauma to the extensor mechanism were excluded. Two raters measured the IS, CDI, PTI, SPE, LCI, and knee flexion angle (KFA) on MRI. Interobserver reliability and correlation between measurements were calculated. RESULTS: In total, 71 knees were included. PTI (0.73), SPE (0.836), LCI (0.701), and KFA (0.8) demonstrated good- to near-excellent interobserver reliability. IS (0.65) and CDI (0.66) demonstrated moderate interobserver reliability. PTI and SPE showed the strongest significant correlation (0.8112, P = 2.2 × 10-16). IS and CD (0.39, P = .0007) showed a moderate significant correlation. PTI and KFA (0.53, P = 1.685 × 10-6) and SPE and KFA (0.61, P = 1.991 × 10-8) had a significant moderate correlation. LCI and KFA (-0.37, P = .0017) showed a significant moderate negative correlation. All other measurement indices correlated poorly and were insignificant. A total of 94.4% of the knees were defined as having patella alta using IS, with the remaining 5.6% having a raised CDI. Only 14% of cases had an IS of >1.2, a CDI >1.2, and a PTI <0.125, which increased to 39% (28/71) when the threshold for PTI was increased to <0.28. CONCLUSIONS: There was no correlation between tibial (IS and CD) and femoral methods (PTI and SPE) of quantifying patella alta. PTI and SPE did not correlate with trochlea length as measured by LCI. PTI, SPE, and LCI are significantly affected by the KFA during MRI. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic radiographic investigation.

The Upscale Manufacture of Chondrocytes for Allogeneic Cartilage Therapies.

Allogeneic chondrocyte therapies need to be developed to allow more individuals to be treated with a cell therapy for cartilage repair and to reduce the burden and cost of the current two-stage autologous procedures. Upscale manufacture of chondrocytes using a bioreactor could help provide an off-the-shelf allogeneic chondrocyte therapy with many doses being produced in a single manufacturing run. In this study, we assess a good manufacturing practice-compliant hollow-fiber bioreactor (Quantum®) for adult chondrocyte manufacture. Chondrocytes were isolated from knee arthroplasty-derived cartilage (n = 5) and expanded in media supplemented with 10% fetal bovine serum (FBS) or 5% human platelet lysate (hPL) on tissue culture plastic (TCP) for a single passage. hPL-supplemented cultures were then expanded in the Quantum bioreactor for a further passage. Matched, parallel cultures in hPL or FBS were maintained on TCP. Chondrocytes from all culture conditions were characterized in terms of growth kinetics, morphology, immunoprofile, chondrogenic potential (chondrocyte pellet assays), and single telomere length analysis. Quantum expansion of chondrocytes resulted in 86.4 ± 38.5 × 106 cells in 8.4 ± 1.5 days, following seeding of 10.2 ± 3.6 × 106 cells. This related to 3.0 ± 1.0 population doublings in the Quantum bioreactor, compared with 2.1 ± 0.6 and 1.3 ± 1.0 on TCP in hPL- and FBS-supplemented media, respectively. Quantum- and TCP-expanded cultures retained equivalent chondropotency and mesenchymal stromal cell marker immunoprofiles, with only the integrin marker, CD49a, decreasing following Quantum expansion. Quantum-expanded chondrocytes demonstrated equivalent chondrogenic potential (as assessed by ability to form and maintain chondrogenic pellets) with matched hPL TCP populations. hPL manufacture, however, led to reduced chondrogenic potential and increased cell surface positivity of integrins CD49b, CD49c, and CD51/61 compared with FBS cultures. Quantum expansion of chondrocytes did not result in shortened 17p telomere length when compared with matched TCP cultures. This study demonstrates that large numbers of adult chondrocytes can be manufactured in the Quantum hollow-fiber bioreactor. This rapid, upscale expansion does not alter chondrocyte phenotype when compared with matched TCP expansion. Therefore, the Quantum provides an attractive method of manufacturing chondrocytes for clinical use. Media supplementation with hPL for chondrocyte expansion may, however, be unfavorable in terms of retaining chondrogenic capacity.

A comprehensive review of quantum bioreactor cell manufacture: Research and clinical applications.

The Quantum cell expansion system manufactured by Terumo-BCT is perhaps the most widely reported Good Manufacturing Practice-compliant bioreactor used for the expansion of adherent cell populations, both for research purposes and clinical cell-based therapies/trials. Although the system was originally designed for adherent cell expansion, more recently suspension cultures and extracellular vesicle manufacturing protocols have been published using the Quantum system. Cell therapy research and regenerative medicine in general is a rapidly expanding field and as such it is likely that the use of this system will become even more widespread and perhaps mandatory, for both research and development and in the clinic. The purpose of this review is to describe, compare and discuss the diverse range of research and clinical applications currently using the Quantum system, which to our knowledge has not previously been reviewed. In addition, current and future challenges will also be discussed.