TY  - JOUR
A1  - Bothe, Friederike
A1  - Deubel, Anne-Kathrin
A1  - Hesse, Eliane
A1  - Lotz, Benedict
A1  - Groll, Jürgen
A1  - Werner, Carsten
A1  - Richter, Wiltrud
A1  - Hagmann, Sebastien
T1  - Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs
JF  - International Journal of Molecular Sciences
N2  - Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.
KW  - cartilage repair
KW  - osteochondral defect
KW  - tissue engineering
KW  - starPEG hydrogel
KW  - chondrocyte
KW  - MSC
KW  - zonal construct
KW  - minipig
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285118
SN  - 1422-0067
VL  - 20
IS  - 3
ER  - 
TY  - JOUR
A1  - Herrmann, Marietta
A1  - Hildebrand, Maria
A1  - Menzel, Ursula
A1  - Fahy, Niamh
A1  - Alini, Mauro
A1  - Lang, Siegmund
A1  - Benneker, Lorin
A1  - Verrier, Sophie
A1  - Stoddart, Martin J.
A1  - Bara, Jennifer J.
T1  - Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human iliac crest, vertebral body and femoral head
JF  - International Journal of Molecular Sciences
N2  - (1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14–91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45−CD34−CD73+, CD45−CD34−CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.
KW  - bone marrow stromal cells
KW  - MSC
KW  - pericytes
KW  - femoral head
KW  - vertebral body
KW  - iliac crest
KW  - chondrogenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285054
SN  - 1422-0067
VL  - 20
IS  - 14
ER  -