Critical Analytics for Manufacturing Personalised-Medicine (CAMP) Interdisciplinary Research Group (IRG), Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore 138602, Singapore.
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119288, Singapore.
Int J Mol Sci. 2024 Oct 2;25(19):10627. doi: 10.3390/ijms251910627.
Mesenchymal stromal cells (MSCs) are promising candidates for cartilage repair therapy due to their self-renewal, chondrogenic, and immunomodulatory capacities. It is widely recognized that a shift from fetal bovine serum (FBS)-containing medium toward a fully chemically defined serum-free (SF) medium would be necessary for clinical applications of MSCs to eliminate issues such as xeno-contamination and batch-to-batch variation. However, there is a notable gap in the literature regarding the evaluation of the chondrogenic ability of SF-expanded MSCs (SF-MSCs). In this study, we compared the in vivo regeneration effect of FBS-MSCs and SF-MSCs in a rat osteochondral defect model and found poor cartilage repair outcomes for SF-MSCs. Consequently, a comparative analysis of FBS-MSCs and SF-MSCs expanded using two SF media, MesenCult™-ACF (ACF), and Custom StemPro™ MSC SFM XenoFree (XF) was conducted in vitro. Our results show that SF-expanded MSCs constitute variations in morphology, surface markers, senescence status, differentiation capacity, and senescence/apoptosis status. Highly proliferative MSCs supported by SF medium do not always correlate to their chondrogenic and cartilage repair ability. Prior determination of the SF medium's ability to support the chondrogenic ability of expanded MSCs is therefore crucial when choosing an SF medium to manufacture MSCs for clinical application in cartilage repair.
间充质基质细胞 (MSCs) 因其自我更新、软骨生成和免疫调节能力而成为软骨修复治疗的有前途的候选者。人们普遍认为，为了将 MSCs 的临床应用从含胎牛血清 (FBS) 的培养基转变为完全化学定义的无血清 (SF) 培养基，有必要消除异种污染和批次间差异等问题。然而，关于 SF 扩增的 MSCs (SF-MSCs) 的软骨生成能力的评估，文献中存在明显的差距。在这项研究中，我们比较了 FBS-MSCs 和 SF-MSCs 在大鼠骨软骨缺损模型中的体内再生效果，发现 SF-MSCs 的软骨修复效果较差。因此，我们对使用两种 SF 培养基，即 MesenCult™-ACF (ACF) 和 Custom StemPro™ MSC SFM XenoFree (XF) 扩增的 FBS-MSCs 和 SF-MSCs 进行了体外比较分析。我们的结果表明，SF 扩增的 MSCs 在形态、表面标志物、衰老状态、分化能力和衰老/凋亡状态方面存在差异。SF 培养基支持的高增殖性 MSCs 并不总是与其软骨生成和软骨修复能力相关。因此，在选择 SF 培养基来制造用于软骨修复的临床应用的 MSCs 时，确定 SF 培养基支持扩增的 MSCs 的软骨生成能力非常重要。
