The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage
Pleumeekers, MM and Nimeskern, L and Koevoet, WLM and Kops, N and Poublon, RML and Stok, KS and van Osch, GJVM, The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage, European Cells and Materials, 27 pp. 264-280. ISSN 1473-2262 (2014) [Refereed Article]
Cartilage has limited self-regenerative capacity. Tissue
engineering can offer promising solutions for reconstruction
of missing or damaged cartilage. A major challenge herein
is to define an appropriate cell source that is capable of
generating a stable and functional matrix. This study
evaluated the performance of culture-expanded human
chondrocytes from ear (EC), nose (NC) and articular joint
(AC), as well as bone-marrow-derived and adipose-tissuederived mesenchymal stem cells both in vitro and in vivo.
All cells (≥ 3 donors per source) were culture-expanded,
encapsulated in alginate and cultured for 5 weeks.
Subsequently, constructs were implanted subcutaneously
for 8 additional weeks. Before and after implantation,
glycosaminoglycan (GAG) and collagen content were
measured using biochemical assays. Mechanical properties
were determined using stress-strain-indentation tests.
Hypertrophic differentiation was evaluated with qRT-PCR
and subsequent endochondral ossification with histology.
ACs had higher chondrogenic potential in vitro than the
other cell sources, as assessed by gene expression and GAG
content (p < 0.001). However, after implantation, ACs did
not further increase their matrix. In contrast, ECs and NCs
continued producing matrix in vivo leading to higher GAG
content (p < 0.001) and elastic modulus. For NC-constructs,
matrix-deposition was associated with the elastic modulus
(R2 = 0.477, p = 0.039). Although all cells – except ACs –
expressed markers for hypertrophic differentiation in vitro,
there was no bone formed in vivo. Our work shows that
cartilage formation and functionality depends on the cell
source used. ACs possess the highest chondrogenic capacity
in vitro, while ECs and NCs are most potent in vivo, making
them attractive cell sources for cartilage repair.