Optimizing bone marrow harvesting sites for enhanced mesenchymal stem cell yield and efficacy in knee osteoarthritis treatment

Table 4 Challenges and limitations in isolation and characterization of bone marrow

Challenges/limitations	Proposed solutions	Research gaps	Future directions
Lower MSC yield from alternative sites (distal femur, proximal tibia)	Optimize harvesting techniques at alternative sites to enhance MSC yield and viability	Lack of comprehensive comparative studies of MSC yield from different anatomical sites	Prioritize large-scale, randomized controlled trials across multiple anatomical sites
Necessity of larger volumes or in vitro expansion due to low yield	Refinements in aspiration technique and improvements in instruments	Limited data on long-term efficacy and safety of MSC-based therapies	Focus on personalized harvesting strategies based on biomarkers and patient characteristics
Influence of patient-specific factors (age and bone quality)	Develop protocols that combine cells from multiple sites for therapeutic dose	The absence of standardized protocols leads to variability in outcomes	Explore the integration of bone marrow harvesting techniques with emerging technologies (three-dimensional bioprinting, gene editing)
Variability in MSC yield and success rates across patients	Conduct large-scale comparative studies evaluating MSC yield, viability, and regenerative potential	Insufficient exploration of alternative harvesting sites for applications beyond knee osteoarthritis	Develop bioengineered scaffolds to enhance MSC survival and differentiation
Absence of standardized aspiration protocols for different sites	Establish standardized bone marrow aspiration protocols	Limited understanding of MSC functional heterogeneity from different sites	Investigate pre-operative and post-operative strategies to minimize complications
Complications at alternative sites (e.g., cortical bone fracture)	Explore less invasive harvesting techniques to reduce morbidity	Lack of personalized strategies considering genetic background, age, and disease state	Use advanced techniques (single-cell RNA sequencing, proteomics) to assess MSC characteristics
Donor-site morbidity from iliac crest harvesting	Innovate with rotational aspiration devices and powered biopsy systems
Age and health-related limitations (osteoporosis, lower MSC density)	Investigate personalized approaches based on patient-specific factors
Long-term efficacy and safety of MSC therapies not fully studied	Include extended follow-up in studies to assess long-term efficacy and safety

MSC: Mesenchymal stem cell.