Human bone marrow-derived mesenchymal stromal cells (MSCs) have been investigated in numerous disease settings involving impaired regeneration because of the crucial role they play in tissue maintenance and repair. Considering the number of comorbidities associated with type 2 diabetes mellitus (T2DM), the hypothesis that MSCs mediate these comorbidities via a reduction in their native maintenance and repair activities is an intriguing line of inquiry. Here, it is demonstrated that the number of bone marrow-derived MSCs in people with T2DM was reduced compared to that of age-matched control (AMC) donors and that this was due to a specific decrease in the number of MSCs with osteogenic capacity. There were no differences in MSC cell surface phenotype or in MSC expansion, differentiation, or angiogenic or migratory capacity from donors living with T2DM as compared to AMCs. These findings elucidate the basic biology of MSCs and their potential as mediators of diabetic comorbidities, especially osteopathies, and provide insight into donor choice for MSC-based clinical trials. This study suggests that any role of bone marrow MSCs as a mediator of T2DM comorbidity is likely due to a reduction in the osteoprogenitor population size and not due to a permanent alteration to the MSCs’ capacity to maintain tissue homeostasis through expansion and differentiation.

Spinal cord injury (SCI) is a devastating trauma that can cause permanent disability, life-long chronic issues for sufferers and is a big socioeconomic burden. Regenerative medicine aims to overcome injury caused deficits and restore function after SCI through gene therapy and tissue engineering approaches. SCI has a multifaceted pathophysiology. Due to this, producing therapies that target multiple different cellular and molecular mechanisms might prove to be a superior approach in attempts at regeneration. Both biomaterials and nucleic acid delivery via lentiviral vectors (LVs) have proven to promote repair and restoration of function post SCI in animal models. Studies indicate that a combination of biomaterials and LVs is more effective than either approach alone. This review presents studies supporting the use of LVs and LVs delivered with biomaterials in therapies for SCI and summarises methods to combine LVs with biomaterials for SCI treatment. By summarising this knowledge this review aims to demonstrate how LV delivery with biomaterials can augment/compliment both LV and biomaterial therapeutic effects in SCI.

Aim: Osteoporosis (OP) is caused by imbalanced bone remodelling homeostasis. It is highly prevalent, especially in post-menopausal women, resulting in high risk of fracture and morbidity. Mesenchymal stromal cells (MSCs) are osteoblast progenitors, and orchestrate the function of surrounding cells including osteoblasts. Understanding MSC phenotype and function is therefore critical in discerning the aetiology of OP and developing superior therapies. Currently, adequate long-term therapeutic strategies are not available. Methods: Bioinformatic analysis of ribonucleic acid sequencing (RNA-seq) data revealed differential expression of genes primarily related to osteogenic differentiation and proliferation, followed by confirmatory in vitro analysis. Results: This study identified novel and previously proposed targets for therapeutic intervention in OP. Functional assessment demonstrated reduced MSC number and osteogenic capacity associated with OP. Proliferation was not affected but OP was unexpectedly associated with a reduction in MSC adipogenic differentiation capacity, correlating with donor age. Conclusions: These data indicate specific targets for further studies of future treatments for OP, including the assessment of modified MSCs as therapeutics. Advances in this area may contribute to reducing fracture-associated morbidity and mortality, and improving quality of life for the 200 million people living with OP globally.