Ongoing studies of cell-based therapies for articular cartilage defects in Japan

Figures & data

Figure 1 Treatment criteria, technical significance, and benefits.

Abbreviations: ACI, autologous chondrocyte implantation; MF, microfracture; OAT, osteochondral autograft transplant.

Table 1 Clinical research showing improved autologous chondrocyte implantation

Reference	Patients, n	Age,^a years	F/U, years	Etiology	Defect size (cm^Citation2) and location	Cell number (×10^6)	Lysholm score before and after surgery	Histologic/biomechanical findings	Graft failure rate (type)/clinical complication
Ochi et al^Citation30	28	26	2	Trauma 57% OCD 32% OA 7% Chondromalacia patella 4%	3.0 (0.7-16.0) MFC 46% LFC 46% Patella 8%	2.75 (0.4–42)	7l±l2/97±5 (P<0.001), 2 years	Hyaline-like cartilage with integration 1 year (n=1), 6 months (n=1) Hardness: similar to that of the surrounding cartilage (1 year, 2 years)	25% Hypertrophy (n=3); partial periosteum detachment (n=3); partial graft ossification (n=1)/crepitus and occasional discomfort (n=3)
Tohyama^Citation38	27	N/A	2	Trauma 70% OCD 11% OA 19%	3.2 (1.2–9.4) MFC 59% LFC 19% Patella 6%	N/A	60.0±l3.7/89.8±9.5 (P<0.00l), 2 years	N/A	7.4% Hypertrophy and detachment (n=1); partial detachment (n=1)/restricted range of motion (n=1)
Adachi et al^Citation37	73	25	1, 2, >5	Trauma 56% OCD 33% Recurrent patella dislocation 5% OA 3%	3.6 (2.0–16.0) MFC 45% LFC 34%, Patella 21%	2.2 (0.4–42)	N/A	ICRS II scale: 70.4±20.8, ECM: strongly stained with safranin O Not normal layer (1 year; n=40) Hardness: femoral condyle, similar to surrounding cartilage; patellar lesion, significantly decreased compared with femoral condyle (2 years)	30% Hypertrophy was most common/N/A

Note:

a Average age at the time of surgery.

Abbreviations: F/U, follow-up; OCD, osteochondritis dissecans; OA, osteoarthritis; MFC, medial femoral condyle; LFC, lateral femoral condyle; N/A not applicable; ICRS, International Cartilage Repair Society; ECM, extracellular matrix.

Table 2 Clinical study of cartilage regeneration with bone marrow-derived MSCs

Reference	Study	n	F/U	Mean age, years	Etiology	Rehabilitation	Clinical outcomes	Macroscopic findings	Histologic findings	MRI findings
Wakitani et al^Citation64	Case control + HTO with/ without cells	12/12	16 months	63	OA	4 days, CPM 6 weeks, PWB 8 weeks, FWB	HSS not significantly different	Greater score in MSC	MSC > no-cell	None
Wakitani et al^Citation62	Prospective case	2	5 years, 9 months, 4 years	26 44	Trauma (chronic)	3 days, CPM 3 weeks, PWB 6 weeks, FWB	Satisfied but show slightly limited knee motion score (–)	Cartilage-like tissue	Fibrocartilage (1 year)	None
Wakitani et al^Citation63	Prospective case	3	17–27 months	31 44 45	Chronic cartilage lesions	3 days, CPM 3 weeks, FWB	IK DC improved	Cartilage-like tissue	Cartilaginous matrix (11 months)	Complete coverage/less intensity than normal
Kuroda^Citation65	Case report (athlete)	1	1 year	31	Trauma	11 days, CPM 4 weeks, PWB 8 weeks, FWB	Return to preinjury level activities with no pain	Smooth tissues (7 months)	Hyaline-like cartilage + collagen type 2 (7 months)	Focal chondral/subchondral irregularities

Abbreviations: F/U, follow-up; HTO, high tibial osteotomy; OA, osteoarthritis; CPM, continuous passive motion; FWB, full weight bearing; PWB, partial weight bearing; HSS, Hospital for Special Surgery; IKDC, International Knee Documentation Committee; MRI, magnetic resonance imaging; MSC, mesenchymal stem cell.

Figure 2 New approval system for commercialization of cell therapy products.

Newman AP. Articular cartilage repair. Am J Sports Med. 1998;26(2):309–324.

 PubMed Web of Science ®Google Scholar

Ochi M, Uchio Y, Kawasaki K, Wakitani S, Iwasa J. Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg Br. 2002;84(4):571–578.

 PubMedGoogle Scholar

Tohyama H, Yasuda K, Minami A, et al. Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan. J Orthop Sci. 2009;14(5):579–588.

 PubMed Web of Science ®Google Scholar

Adachi N, Ochi M, Deie M, et al. Implantation of tissue-engineered cartilage-like tissue for the treatment for full-thickness cartilage defects of the knee. Knee Surg Sports Traumatol Arthrosc. 2014;22(6):1241–1248.

 Web of Science ®Google Scholar

Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10(3):199–206.

 PubMed Web of Science ®Google Scholar

Wakitani S, Mitsuoka T, Nakamura N, Toritsuka Y, Nakamura Y, Horibe S. Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transplant. 2004;13(5):595–600.

 PubMed Web of Science ®Google Scholar

Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007;1(1):74–79.

 PubMed Web of Science ®Google Scholar

Kuroda R, Ishida K, Matsumoto T, et al. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15(2):226–231.

 PubMed Web of Science ®Google Scholar