Department of Biomedical Engineering, Lerner Research Institute (V.P.M., C.B., W.B., and G.F.M), Department of Health Science (I.B.), and Department of Orthopedic Surgery (N.S.P. and G.F.M.), Cleveland Clinic, Cleveland, Ohio.
J Bone Joint Surg Am. 2021 Sep 1;103(17):1628-1636. doi: 10.2106/JBJS.20.02055.
Connective tissue progenitors (CTPs) resident in native tissues serve as biological building blocks in tissue repair and remodeling processes. Methods for analysis and reporting on CTP quantity and quality are essential for defining optimal cell sources and donor characteristics and the impact of cell processing methods for cell therapy applications. The present study examines the influence of donor characteristics and cell concentration (nucleated cells/mL) on CTP prevalence (CTPs/million nucleated cells) and CTP concentration (CTPs/mL) in bone marrow aspirates (BMAs).
Iliac crest bone marrow was aspirated from 436 patients during elective total knee or hip arthroplasty. Bone marrow-derived nucleated cells were plated at a density of 1.19 × 105 cells/cm2. Colony-forming unit analysis was performed on day 6.
Large variation was seen between donors. Age (p < 0.05) and cell concentration (p < 0.001) significantly influenced CTP prevalence and CTP concentration. For every 1-year increase in age, the odds of having at least an average CTP prevalence and CTP concentration decreased by 1.5% and 1.6%, respectively. For every 1 million cells/mL increase in cell concentration, the odds of having at least an average CTP prevalence and CTP concentration increased by 2.2% and 7.9%, respectively. Sex, race, body mass index (BMI), and the presence of osteoporosis did not influence CTP prevalence or CTP concentration.
BMA-derived CTPs were obtained from all patient groups. CTP prevalence and CTP concentration decreased with age. Cell concentration decreased with age and positively correlated with total CTP prevalence and CTP concentration. The mean CTP concentration in patients >60 years of age was a third of the CTP concentration in patients <30 years of age.
Proper BMA techniques are necessary to obtain a high-quality yield and composition of cells and CTPs. The reduced CTP concentration and CTP prevalence in the elderly may be mitigated by the use of cell processing methods that increase CTP concentration and CTP prevalence (e.g., by removing red blood cells, serum, and non-CTPs or by increasing aspirate volumes). Cell concentration in the BMA can be measured at the point of care and is an appropriate initial assessment of the quality of BMA.
存在于原生组织中的结缔组织祖细胞（CTPs）是组织修复和重塑过程中的生物构建块。分析和报告 CTP 数量和质量的方法对于确定最佳细胞来源和供体特征以及细胞处理方法对细胞治疗应用的影响至关重要。本研究探讨了供体特征和细胞浓度（核细胞/mL）对骨髓抽吸物（BMAs）中 CTP 流行率（CTPs/百万核细胞）和 CTP 浓度（CTPs/mL）的影响。
在择期全膝关节或髋关节置换术期间，从 436 名患者的髂嵴骨抽吸骨髓。将骨髓源性核细胞以 1.19×105 个细胞/cm2 的密度接种。第 6 天进行集落形成单位分析。
供体之间存在很大差异。年龄（p<0.05）和细胞浓度（p<0.001）显著影响 CTP 流行率和 CTP 浓度。年龄每增加 1 岁，至少具有平均 CTP 流行率和 CTP 浓度的可能性分别降低 1.5%和 1.6%。细胞浓度每增加 100 万个细胞/mL，至少具有平均 CTP 流行率和 CTP 浓度的可能性分别增加 2.2%和 7.9%。性别、种族、体重指数（BMI）和骨质疏松症的存在均不影响 CTP 流行率或 CTP 浓度。
从所有患者群体中获得了骨髓衍生的 CTPs。CTP 流行率和 CTP 浓度随年龄增长而降低。细胞浓度随年龄增长而降低，与总 CTP 流行率和 CTP 浓度呈正相关。60 岁以上患者的平均 CTP 浓度是 30 岁以下患者 CTP 浓度的三分之一。
适当的骨髓抽吸技术对于获得高质量的细胞和 CTP 产量和组成是必要的。老年人 CTP 浓度和 CTP 流行率降低，可以通过使用增加 CTP 浓度和 CTP 流行率的细胞处理方法来缓解（例如，通过去除红细胞、血清和非 CTPs 或通过增加抽吸体积）。在护理点可以测量骨髓抽吸物中的细胞浓度，并且是评估骨髓抽吸物质量的适当初始评估。
