Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them.

Study Design: Meta-analysis. Objectives: We aimed to analyze the impact of cultured expansion of autologous mesenchymal stromal cells (MSCs) in the management of osteoarthritis of the knee from randomized controlled trials (RCTs) available in the literature. Materials and Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library until August 2021 for RCTs analyzing the efficacy and safety of culture-expanded compared to non-cultured autologous MSCs in the management of knee osteoarthritis. The Visual Analog Score (VAS) for pain, Western Ontario McMaster University’s Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the analyzed outcomes. Analysis was performed in R-platform using OpenMeta [Analyst] software. Results: Overall, 17 studies involving 767 patients were included for analysis. None of the studies made a direct comparison of the culture expanded and non-cultured MSCs, hence we pooled the results of all the included studies of non-cultured and cultured types of MSC sources and made a comparative analysis of the outcomes. At six months, culture expanded MSCs showed significantly better improvement (p < 0.001) in VAS outcome. Uncultured MSCs, on the other hand, demonstrated significant VAS improvement in the long term (12 months) in VAS (p < 0.001), WOMAC (p = 0.025), KOOS score (p = 0.016) where cultured-expanded MSCs failed to demonstrate a significant change. Culturing of MSCs did not significantly increase the complications noted (p = 0.485). On sub-group analysis, adipose-derived uncultured MSCs outperformed culture-expanded MSCs at both short term (six months) and long term (12 months) in functional outcome parameters such as WOMAC (p < 0.001, p = 0.025), Lysholm (p < 0.006), and KOOS (p < 0.003) scores, respectively, compared to their controls. Conclusions: We identified a void in literature evaluating the impact of culture expansion of MSCs for use in knee osteoarthritis. Our indirect analysis of literature showed that culture expansion of autologous MSCs is not a necessary factor to obtain superior results in the management of knee osteoarthritis. Moreover, while using uncultured autologous MSCs, we recommend MSCs of adipose origin to obtain superior functional outcomes. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the need for culture expansion of MSCs for use in cellular therapy of knee osteoarthritis.

Tuberculosis (TB) affection of foot appears to be a rare clinical entity and accounts for <10% and 0.1-0.3% of osteoarticular and extrapulmonary TB, respectively. In TB foot, tarsal joints and calcaneum are more commonly affected followed by talus, distal end of first metatarsal, navicular, cuneiforms, and cuboid bones. A 24-year-old female presented with pain and swelling over dorsum of the left foot from the past 8 months. On examination, there was a diffuse round shaped, solitary swelling measuring about 3.5 cm × 2.5 cm (approx.) with its surface smooth, non-pulsatile, non-fluctuant, non-transilluminant, non-compressible, and non-reducible present over dorsum of the left foot. Radiographic investigations revealed osteolytic lesion over the base of 3rd, 4th, and 5th metatarsals, middle and lateral cuneiforms and cuboid bones along with soft tissue swelling and diffuse transient osteopenia. Under spinal anesthesia, trucut biopsy of the mass revealed paucibacillary type of TB in histopathological examination. The patient was provided with ATT drugs in the form of intensive phase drugs (HRZE) daily for 4 months and continuation phase drugs (HRE) daily for 10 months according to the weight of the patient. The patient was followed up with erythrocyte sedimentation rate and C-reactive protein every 2 months once. The patient achieved a normal range of movements in the midtarsal joints except for the painful terminal range of movements. The patient was still under our follow-up. The cuboid is the second most involved tarsal bone. The diagnosis is not always frankly evident, and a high index of suspicion has to be maintained. Surgical intervention should be limited to biopsy only as multidrug chemotherapy alone is sufficient to achieve complete healing.