Evaluation of Intra-Articular Mesenchymal Stem Cells to Augment Healing of Microfractured Chondral Defects

doi:10.1016/j.arthro.2011.06.002

Arthroscopy: The Journal of Arthroscopic & Related Surgery

Volume 27, Issue 11, November 2011, Pages 1552-1561

https://doi.org/10.1016/j.arthro.2011.06.002 Get rights and content

Purpose

This study evaluated intra-articular injection of bone marrow–derived mesenchymal stem cells (BMSCs) to augment healing with microfracture compared with microfracture alone.

Methods

Ten horses (aged 2.5 to 5 years) had 1-cm² defects arthroscopically created on both medial femoral condyles of the stifle joint (analogous to the human knee). Defects were debrided to subchondral bone followed by microfracture. One month later, 1 randomly selected medial femorotibial joint in each horse received an intra-articular injection of either 20 × 10⁶ BMSCs with 22 mg of hyaluronan or 22 mg of hyaluronan alone. Horses were confined for 4 months, with hand walking commencing at 2 weeks and then increasing in duration and intensity. At 4 months, horses were subjected to strenuous treadmill exercise simulating race training until completion of the study at 12 months. Horses underwent musculoskeletal and radiographic examinations bimonthly and second-look arthroscopy at 6 months. Horses were euthanized 12 months after the defects were made, and the affected joints underwent magnetic resonance imaging and gross, histologic, histomorphometric, immunohistochemical, and biochemical examinations.

Results

Although there was no evidence of any clinically significant improvement in the joints injected with BMSCs, arthroscopic and gross evaluation confirmed a significant increase in repair tissue firmness and a trend for better overall repair tissue quality (cumulative score of all arthroscopic and gross grading criteria) in BMSC-treated joints. Immunohistochemical analysis showed significantly greater levels of aggrecan in repair tissue treated with BMSC injection. There were no other significant treatment effects.

Conclusions

Although there was no significant difference clinically or histologically in the 2 groups, this study confirms that intra-articular BMSCs enhance cartilage repair quality with increased aggrecan content and tissue firmness.

Clinical Relevance

Clinical use of BMSCs in conjunction with microfracture of cartilage defects may be potentially beneficial.

Section snippets

Experimental Design

Ten skeletally mature horses, free of musculoskeletal abnormalities, were entered into this 12-month study. We performed a power calculation based on a previous study with microfractured defects, and n = 10 provided a power of 81% based on this previous study.¹⁰

Defects measuring 1 cm² were arthroscopically created on the medial femoral condyle of both medial femorotibial joints of the stifle joints (analogous to the human knee) as previously described.8, 9 Defects were debrided through the

Musculoskeletal Examinations

On average throughout the study, BMSC + HA limbs were graded with slight pain (1.3 ± 0.08) compared with OHA limbs (1.3 ± 0.08), but there was no significant effect of treatment. The degree of lameness changed over the study period (P < .0001). On average throughout the study, the degree of effusion was slight to mild in both the BMSC + HA–treated joints (1.7 ± 0.01) and OHA-treated joints (1.7 ± 0.01), and there was no significant effect of treatment. On average throughout the study, the

Discussion

Microfracture has been previously shown to enhance the amount of repair tissue in full-thickness articular cartilage defects on the medial femoral condyle in the horse, and type II collagen content is significantly increased.8, 9 It has also been shown that removal of calcified cartilage with retention of the subchondral bone plate in microfractured defects increased the overall amount of repair tissue as assessed by arthroscopic (4 months) and gross evaluation (12 months); furthermore, there

Conclusions

There were no significant clinical improvements or histologic differences between the groups. It is noteworthy that there was statistically significant enhancement in repair tissue firmness and repair quality based on improved aggrecan staining after intra-articular administration of bone marrow–derived culture-expanded MSCs. However, the clinical significance of these findings is yet to be established. Our hypothesis was affirmed in part.

Acknowledgment

The authors acknowledge the staff at the Orthopaedic Research Center, Colorado State University.

References (27)

J.R. Steadman et al.
Outcomes of microfracture for traumatic chondral defects of the knee: Average 11-year follow-up
Arthroscopy
(2003)
P.J. Millett et al.
Outcomes of full-thickness articular cartilage injuries of the shoulder treated with microfracture
Arthroscopy
(2009)
Y. Izuta et al.
Meniscal repair using bone marrow-derived mesenchymal stem cells: Experimental study using green fluorescent protein transgenic rats
Knee
(2005)
K.Y. Saw et al.
Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: An experimental study in a goat model
Arthroscopy
(2009)
S.C. Pitchford et al.
Differential mobilization of subsets of progenitor cells from the bone marrow
Cell Stem Cell
(2009)
P.W. Kopesky et al.
Adult equine bone marrow stromal cells produce a cartilage-like ECM mechanically superior to animal-matched adult chondrocytes
Matrix Biol
(2010)
J.R. Steadman et al.
Microfracture chondroplasty: Indications, techniques, and outcomes
Sports Med Arthrosc Rev
(2003)
J.R. Steadman et al.
Microfracture to treat full-thickness chondral defects: Surgical technique, rehabilitation, and outcomes
J Knee Surg
(2002)
J.R. Steadman et al.
Debridement and microfracture for full-thickness articular cartilage defects
J.R. Steadman et al.
Microfracture: Its history and experience of the developing surgeon
Cartilage
(2010)

A. Bedi et al.

Management of articular cartilage defects of the knee

J Bone Joint Surg Am

(2010)

D.D. Frisbie et al.

Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses

Vet Surg

(1999)

D.D. Frisbie et al.

Early events in cartilage repair after subchondral bone microfracture

Clin Orthop Relat Res

(2003)

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: Supported by the Steadman Philippon Research Institute and Colorado State University Orthopaedic Research Center discretionary funds. C.W.M., D.D.F., J.D.K., and C.E.K. are shareholders in Advanced Regenerative Therapies (ART), which cultures the mesenchymal stem cells.

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Original ArticleEvaluation of Intra-Articular Mesenchymal Stem Cells to Augment Healing of Microfractured Chondral Defects

Purpose

Methods

Results

Conclusions

Clinical Relevance

Section snippets

Experimental Design

Musculoskeletal Examinations

Discussion

Conclusions

Acknowledgment

Arthroscopy

Arthroscopy

Knee

Arthroscopy

Cell Stem Cell

Matrix Biol

Microfracture chondroplasty: Indications, techniques, and outcomes

Sports Med Arthrosc Rev

Microfracture to treat full-thickness chondral defects: Surgical technique, rehabilitation, and outcomes

J Knee Surg

Debridement and microfracture for full-thickness articular cartilage defects

Microfracture: Its history and experience of the developing surgeon

Cartilage

Management of articular cartilage defects of the knee

J Bone Joint Surg Am

Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses

Vet Surg

Early events in cartilage repair after subchondral bone microfracture

Clin Orthop Relat Res

Original Article
Evaluation of Intra-Articular Mesenchymal Stem Cells to Augment Healing of Microfractured Chondral Defects