Background:

Cell-based therapy for cartilage repair is a promising approach and is becoming an established technique. Yet, there is no consensus on the optimal cell source.

Purpose:

To provide a donor-matched quantitative comparison of the connective tissue progenitors (CTPs) derived from cartilage (Outerbridge grade 1-3 [G1-2-3]), bone marrow aspirate concentrate (BMC), infrapatellar fat pad (IPFP), synovium, and periosteum with respect to (1) cell concentration ([Cell], cells/mL), (2) CTP prevalence (P_CTP, colonies per million cells), and (3) biological performance based on in vitro proliferation potential (cells per colony) colony density, and differentiation potential (expression of negatively charged extracellular matrix: glycosaminoglycan-rich extra cellular matrix [GAG-ECM]).

Study Design:

Descriptive laboratory study.

Methods:

Tissues were obtained from 10 patients undergoing total knee arthroplasty (mean age, 59 years; women, n = 6). Automated quantitative colony-forming unit analysis was used to compare [Cell], P_CTP, and CTP biological performance across tissue sources.

Results:

[Cell] was highest in grade 3 cartilage (P = .002) and BMC (P = .001). Median P_CTP was highest in IPFP (P = .001), synovium (P = .003), and G1-2 cartilage (P = .02). Proliferation was highest in synovium-derived CTPs (P < .001). Median colony density was highest in G1-2-3 (P < .001). Median GAG-ECM was highest in G1-2-3 (P < .001). Within each patient, CTPs derived from all tissues were highly heterogeneous in biological performance as determined by cells per colony, density, and GAG-ECM.

Conclusion:

Tissue sources differ in [Cell], P_CTP, and biological attributes. The data presented in this study suggest that cartilage (G1-2-3) is the preferred tissue source for cartilage repair based on P_CTP and GAG-ECM, followed by synovium, IPFP, BMC, and periosteum. However, due to the heterogeneous mixture of CTPs within each tissue source, there exists a subset of CTPs with biological performance similar to G1-2-3 cartilage, particularly in synovium and IPFP. Performance-based clonal selection and expansion of preferred CTPs and their progeny will potentially lead to improved cell population with predictive future.

Clinical Relevance:

Optimal tissue regeneration strategies will require informed decisions regarding which of the available tissue sources to use. Optimizing cell sourcing in any tissue may require separation of CTPs with preferred attributes from those with less desirable attributes. The heterogeneity manifest in the early stage of colony formation represents an opportunity for performance-based clone selection for clinical cell processing and manufacturing.

中文翻译：

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天然-骨关节炎联合干细胞和祖细胞用于基于软骨细胞的治疗：关于浓度和生物学性能的定量比较。

背景：

基于细胞的软骨修复疗法是一种有前途的方法，并且正在成为一种成熟的技术。然而，关于最佳细胞来源尚无共识。

目的：

为了提供供体匹配的软骨（外桥1-3级[G1-2-3]），骨髓穿刺浓缩液（BMC），pat下脂肪垫（IPFP），滑膜来源的结缔组织祖细胞（CTP）的定量比较，以及骨膜，涉及以下方面：（1）细胞浓度（[细胞]，细胞/ mL），（2）CTP患病率（P _CTP，每百万个细胞的菌落数），以及（3）基于体外增殖潜能的生物性能（细胞菌落密度和分化潜能（带负电荷的细胞外基质表达：富含糖胺聚糖的细胞外基质[GAG-ECM]）。

学习规划：

描述性实验室研究。

方法：

从10例行全膝关节置换术的患者（平均年龄59岁；女性，n = 6）中获取组织。使用自动化的定量菌落形成单位分析来比较[Cell]，P _CTP和CTP在整个组织来源中的生物学性能。

结果：

[细胞]在3级软骨（P = .002）和BMC（P = .001）中最高。中位P _CTP在IPFP（P = .001），滑膜（P = .003）和G1-2软骨（P = .02）中最高。滑膜来源的CTP的增殖最高（P <.001）。G1-2-3中菌落密度最高（P <.001）。GAG-ECM中位数在G1-2-3中最高（P <.001）。在每位患者中，源自所有组织的CTP在生物学性能上高度异质，这取决于每个菌落的细胞数，密度和GAG-ECM。

结论：

组织来源在[细胞]，P _CTP和生物学属性方面有所不同。本研究中提供的数据表明，软骨（G1-2-3）是基于P _CTP和GAG-ECM进行软骨修复的首选组织来源，其次是滑膜，IPFP，BMC和骨膜。但是，由于每种组织来源中CTP的异质混合，因此存在一部分CTP具有与G1-2-3软骨相似的生物学性能，尤其是在滑膜和IPFP中。基于性能的克隆选择和首选CTP及其子代的扩展将潜在地导致具有预期未来的细胞群的改善。

临床相关性：

最佳的组织再生策略将需要就使用哪些可用组织来源做出明智的决定。优化任何组织中的细胞来源可能需要将具有优选属性的CTP与具有较不期望属性的CTP分开。集落形成的早期阶段中的异质性表现为临床细胞加工和生产中基于性能的克隆选择提供了机会。