Abstract：
OBJECTIVE: Autologous tenocyte implantation (OrthoATI™) therapy has demonstrated efficacy in treating patients with tendinopathy at various anatomical sites. This study evaluates the effect of patient age, gender, and tendon biopsy site on morphology, growth, and gene expression of autologous tendon cells used to treat chronic tendinopathy.
METHODS: Patients undergoing OrthoATI™ for tendinopathies between 2020 and 2022 were initially treated by biopsies taken from patella tendon (PT) or palmaris longus tendon (PL). The biopsies were sent to a Good Manufacturing Practice (GMP) cell laboratory where tendon cells were isolated, cultured, and expanded for four to six weeks. Cell morphology was assessed using phase contrast microscopy. Droplet digital PCR (ddPCR) was utilized for gene expression analysis. Dichotomous results were compared between groups using x2 or Fisher\'s exact tests with no adjustment for multiple comparisons. The nonparametric Mann-Whitney U and Kruskal-Wallis tests were utilized for the sex and age (<35y, 35-44y, 45-54y, >55y) analyses, respectively. All analyses were performed using IBM SPSS v27, and a two-tailed P-value of <0.05 was considered statistically significant.
RESULTS: 149 patients were included in the analysis. The PT was biopsied in 63 patients, and PL in 86 patients. There were no observer effects for age and gender between the PT and PL groups. There was no statistical significance between the PT and PL tendons for cell morphology, average cell population doubling time (PDT) (PT 83.9 vs PL 82.7 h, p = 0.482), cellular yield (PT 16.2 vs PL 15.2 × 106, p = 0.099), and cell viability (PT 98.7 vs PL 99.0%, p = 0.277). Additionally, ddPCR analyses showed no statistical significance found in tenogenic gene expression, including collagen type I (COL1, p = 0.86), tenomodulin (TNMD, p = 0.837) and scleraxis (SCX, p = 0.331) between PT- and PL-derived tendon cells. An age stratification analysis found no effect on growth and gene expression. COL1 was found to be higher in males when compared to females (P < 0.001), but otherwise no difference was seen in growth and gene expression in the gender analysis. No postbiopsy clinical complications were reported for either group.
CONCLUSIONS: This study has shown that the growth and bioactivities of tendon cells from tendon biopsies for OrthoATI™ are not affected by tendon donor site and age.
METHODS: IV.
METHODS: Patients undergoing OrthoATI™ for tendinopathies between 2020 and 2022 were initially treated by biopsies taken from patella tendon (PT) or palmaris longus tendon (PL). The biopsies were sent to a Good Manufacturing Practice (GMP) cell laboratory where tendon cells were isolated, cultured, and expanded for four to six weeks. Cell morphology was assessed using phase contrast microscopy. Droplet digital PCR (ddPCR) was utilized for gene expression analysis. Dichotomous results were compared between groups using x2 or Fisher\'s exact tests with no adjustment for multiple comparisons. The nonparametric Mann-Whitney U and Kruskal-Wallis tests were utilized for the sex and age (<35y, 35-44y, 45-54y, >55y) analyses, respectively. All analyses were performed using IBM SPSS v27, and a two-tailed P-value of <0.05 was considered statistically significant.
RESULTS: 149 patients were included in the analysis. The PT was biopsied in 63 patients, and PL in 86 patients. There were no observer effects for age and gender between the PT and PL groups. There was no statistical significance between the PT and PL tendons for cell morphology, average cell population doubling time (PDT) (PT 83.9 vs PL 82.7 h, p = 0.482), cellular yield (PT 16.2 vs PL 15.2 × 106, p = 0.099), and cell viability (PT 98.7 vs PL 99.0%, p = 0.277). Additionally, ddPCR analyses showed no statistical significance found in tenogenic gene expression, including collagen type I (COL1, p = 0.86), tenomodulin (TNMD, p = 0.837) and scleraxis (SCX, p = 0.331) between PT- and PL-derived tendon cells. An age stratification analysis found no effect on growth and gene expression. COL1 was found to be higher in males when compared to females (P < 0.001), but otherwise no difference was seen in growth and gene expression in the gender analysis. No postbiopsy clinical complications were reported for either group.
CONCLUSIONS: This study has shown that the growth and bioactivities of tendon cells from tendon biopsies for OrthoATI™ are not affected by tendon donor site and age.
METHODS: IV.
摘要：
目的：自体肌腱细胞植入（OrthoATI™）疗法已证明在治疗不同解剖部位的肌腱病患者中有效。这项研究评估了患者年龄的影响，形态学上的性别和肌腱活检部位，用于治疗慢性肌腱病的自体肌腱细胞的生长和基因表达。
方法：在2020年至2022年期间接受OrthoATI™治疗肌腱病的患者最初通过从髌腱（PT）或掌长肌腱（PL）进行活检进行治疗。自体肌腱细胞在良好生产规范（GMP）细胞实验室进行处理，在那里他们被分离，培养和扩张四到六周。使用相差显微镜评估细胞形态。利用液滴数字PCR(ddPCR)进行基因表达分析。使用x2或Fisher精确检验对两组之间的二分结果进行比较，不对多重比较进行校正。非参数Mann-WhitneyU和Kruskal-Wallis检验用于性别和年龄（<35岁，35-44y,45-54y,>55y)分别进行分析。所有分析均使用IBMSPSSv27进行，双尾P值<0.05被认为具有统计学意义。
结果：149例患者被纳入分析。对63例患者进行了PT活检，86例患者的PL。PT和PL组之间的年龄和性别没有观察者效应。PT和PL肌腱对细胞形态无统计学意义，平均细胞群倍增时间（PDT）（PT83.9与PL82.7小时，p=0.482),细胞产量（PT16.2对PL15.2×106，p=0.099),和细胞活力(PT98.7vsPL99.0%，p=0.277）。此外,ddPCR分析显示，在包括I型胶原蛋白的张力基因表达中没有发现统计学意义（COL1，p=0.86），腱调节素(TNMD，p=0.837)和巩膜(SCX，P=0.331）在PT和PL衍生的肌腱细胞之间。年龄分层分析发现对生长和基因表达没有影响。与女性相比，男性的COL1水平更高(P<0.001)。但在性别分析中，生长和基因表达没有差异。两组均未报告活检后的临床并发症。
结论：这项研究表明，OrthoATI™的肌腱活检组织的肌腱细胞的生长和生物活性不受肌腱供体部位和年龄的影响。
方法：IV.
方法：在2020年至2022年期间接受OrthoATI™治疗肌腱病的患者最初通过从髌腱（PT）或掌长肌腱（PL）进行活检进行治疗。自体肌腱细胞在良好生产规范（GMP）细胞实验室进行处理，在那里他们被分离，培养和扩张四到六周。使用相差显微镜评估细胞形态。利用液滴数字PCR(ddPCR)进行基因表达分析。使用x2或Fisher精确检验对两组之间的二分结果进行比较，不对多重比较进行校正。非参数Mann-WhitneyU和Kruskal-Wallis检验用于性别和年龄（<35岁，35-44y,45-54y,>55y)分别进行分析。所有分析均使用IBMSPSSv27进行，双尾P值<0.05被认为具有统计学意义。
结果：149例患者被纳入分析。对63例患者进行了PT活检，86例患者的PL。PT和PL组之间的年龄和性别没有观察者效应。PT和PL肌腱对细胞形态无统计学意义，平均细胞群倍增时间（PDT）（PT83.9与PL82.7小时，p=0.482),细胞产量（PT16.2对PL15.2×106，p=0.099),和细胞活力(PT98.7vsPL99.0%，p=0.277）。此外,ddPCR分析显示，在包括I型胶原蛋白的张力基因表达中没有发现统计学意义（COL1，p=0.86），腱调节素(TNMD，p=0.837)和巩膜(SCX，P=0.331）在PT和PL衍生的肌腱细胞之间。年龄分层分析发现对生长和基因表达没有影响。与女性相比，男性的COL1水平更高(P<0.001)。但在性别分析中，生长和基因表达没有差异。两组均未报告活检后的临床并发症。
结论：这项研究表明，OrthoATI™的肌腱活检组织的肌腱细胞的生长和生物活性不受肌腱供体部位和年龄的影响。
方法：IV.
