• avascular necrosis
• hip
• orthobiologics
• osteonecrosis
• regenerative therapies

• Humans
• Femur Head Necrosis/therapy
• Femur Head Necrosis/surgery
• Arthroplasty, Replacement, Hip
• Platelet-Rich Plasma
• Survival Analysis
• Mesenchymal Stem Cell Transplantation

• Bone graft
• Core decompression
• Hip-joint preservation
• Osteonecrosis of the femoral head
• Tissue engineering
• Treatment

• bone homeostasis
• osteonecrosis
• pathogenesis
• therapy

• Humans
• Homeostasis/physiology
• Osteonecrosis/therapy
• Osteonecrosis/physiopathology
• Osteonecrosis/etiology
• Risk Factors
• Bone and Bones
• Osteoclasts/physiology
• Osteoblasts/physiology

• Core decompression
• Femoral head
• Osteonecrosis
• Stem cell

• Humans
• Femur Head Necrosis/therapy
• Male
• Adult
• Mesenchymal Stem Cell Transplantation/methods
• Female
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Retrospective Studies
• Bone Marrow Cells/cytology
• Treatment Outcome
• Cells, Cultured
• Middle Aged
• Transplantation, Autologous
• Decompression, Surgical/methods

• No. 22D0801L1 the Ministry of Science and ICT, the Ministry of Health & Welfare
• No. 22C0604L1 the Ministry of Science and ICT, the Ministry of Health & Welfare
• the Ministry of Science and ICT, the Ministry of Health & Welfare

• Cellular therapy
• Clinical applications
• Fracture healing
• Stem cells

• Humans
• Bone Regeneration/physiology
• Cell- and Tissue-Based Therapy/methods
• Fracture Healing/physiology
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells
• Osteogenesis/physiology

• AKT
• co-culture
• esophageal fibroblasts
• resveratrol
• stem cell
• umbilical cord mesenchymal stem cells

• Humans
• Resveratrol/pharmacology
• Mesenchymal Stem Cells/drug effects
• Mesenchymal Stem Cells/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Cell Differentiation/drug effects
• Fibroblasts/drug effects
• Fibroblasts/metabolism
• Signal Transduction/drug effects
• Umbilical Cord/cytology
• Esophagus/drug effects
• Esophagus/cytology
• Collagen/metabolism
• Cells, Cultured
• Coculture Techniques
• Interleukin-6/metabolism
• Transforming Growth Factor beta/metabolism
• Phosphorylation
• Caspase 9/metabolism

• Guangdong Provincial Department of Science and Technology
• Department of Education of Guangdong Province
• Guangdong Province Medical Products Administration

• Femoral head osteonecrosis
• Hip
• Prognostic factors

• biomaterials
• bone tissue engineering
• osteonecrosis of the femoral head
• regenerative therapy

• National Natural Science Foundation of China

• MSC
• core decompression
• mesenchymal stem cells
• mesenchymal stromal cells
• osteonecrosis of the femoral head

• BMSCs
• MSCs
• Osteonecrosis of the femoral head
• Regenerative medicine
• Treatment
• bone marrow aspirate concentrate (BMAC)
• cell-based therapy
• femoral head
• growth factors
• osteogenic cells
• osteonecrosis of the femoral head (ONFH)
• regenerative therapies
• stem cells

Osteonecrosis of the femoral head (ONFH) is a refractory disease due to its unclear pathomechanism. Therapies during the early stage of ONFH have not achieved satisfactory results. Therefore, this study aims to explore the available evidence for the therapeutic effect of human umbilical cord mesenchymal stem cells (HUCMSCs) on early-stage traumatic ONFH.

Early-stage traumatic ONFH was established. The femoral heads of rats were then locally administered HUCMSCs. Four weeks and eight weeks after surgery, bone repair of the necrotic area in the femoral head was analyzed to evaluate the therapeutic effect of HUCMSCs using micro-CT, histopathological staining, immunofluorescence staining, Luminex.

HUCMSCs were still present in the femoral head four weeks later, and the morphological, micro-CT and histopathological outcomes in the 4-week HUCMSC-treated group were better than those in the model, NS and 8-week HUCMSC-treated groups. Local transplantation of HUCMSCs promoted bone repair and prevented bone loss in the necrotic area of the femoral head.

HUCMSCs can survive and positively affect the femoral head through local transplantation in early-stage traumatic ONFH. The conclusions of this study can provide a treatment option for patients who have ONFH and can serve as basic research on the advanced development of this disease.

The study indicated that the positive effect of exogenous HUCMSCs in the treatment of early-stage traumatic ONFH provides the solid basis and guidance for the clinical application of HUCMSCs.

• osteonecrosis of the femoral head
• hucmscs
• therapeutic effect

Osteonecrosis of the femoral head (ONFH) is a frequent and refractory disease whose pathogenesis has not yet been elucidated. Infection and other factors that reduce the local blood supply can lead to bone necrosis.

To aim of this study was to assess the relationship of ONFH with bone infection by use of metagenomic sequencing.

Twelve patients with idiopathic ONFH and 12 comparable controls who were undergoing hip arthroplasty were followed up in parallel. Necrotic femoral head specimens were collected for bacterial and fungal cultures using standard methods. Bone specimens were subjected to preliminary processing, and metagenomics sequencing of microorganisms was performed. A one-way analysis of variance was used to compare bacterial species in the two groups.

Bacterial and fungal cultures exhibited no evidence of microbial growth in all isolated necrotic femoral head tissues. We thus performed metagenomic sequencing and classified the species as suspected pathogens or suspected background microorganisms based on known bacterial pathogenicity. There was no evidence of viruses, fungi, parasites, M. tuberculosis complex, or mycoplasma/chlamydia. There were also no significant differences in suspected pathogens or suspected background microorganisms (P > 0.05).

Although we found no pathogens specific for ONFH in necrotic femoral head tissue, our research provides a foundation for future research on the metagenomics of bone pathogens.

• Idiopathic
• Osteonecrosis of the femoral head
• Sequencing
• Pathogens

To assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier.

Retrospective study.

University clinical research laboratory.

Patients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment.

A 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation.

Radiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment.

Upon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation.

The 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition.

• Mesenchymal stromal cell
• Osteonecrosis of the femoral head
• Post-collapse
• Vascularised bone graft

• Advanced AVN
• Avascular necrosis
• Bone marrow aspirate concentrate
• Stem cells
• Subchondral collapse
• core decompression

• Benign bone tumors of lower extremity
• Bone defect reconstruction
• Bone marrow mesenchymal stem cell
• Rapid screening–enrichment–composite system

• Osteonecrosis of the femoral head
• affinity cyclic peptide
• bone marrow mesenchymal stem cell
• core decompression
• β-tricalcium phosphate

• bone regeneration
• clinical trial
• expanded MSC
• femoral head osteonecrosis

Osteonecrosis (ON) is an acquired debilitating skeletal disorder, which is caused by a multitude of traumatic and non-traumatic etiological factors. Vascular damage, mechanical stress and increased intraosseous pressure have been discussed as contributors to ON. The optimal treatment of ON remains to be determined, since the current gold standard, core decompression, is insufficiently effective. Specific properties of mesenchymal stromal cells (MSCs) provide the rationale for their assessment in advanced stages of ON: Osteoinductive potential has been demonstrated and MSC preparations of suitable quality for use as medicinal products have been developed. Here we review the scant information on the use of allogeneic or autologous MSCs in advanced ON as well as potentially supportive data from pre-clinical studies with autologous bone marrow mononuclear cells (auto BM-MNCs), which have been studied quite extensively and the presumed therapeutic effect of which was attributed to the rare MSCs contained in these cell products. Outcomes in clinical trials with MSCs and auto-BM-MNCs remain preliminary and non-definitive, at best promising, with respect to their pharmacological effect. Clearly, though, the application of any of these cell therapies was technically feasible and safe in that it was associated with low complication rates. The heterogeneity of cell type and source, study protocols, cell manufacturing, cell properties, cell doses and surgical techniques might contribute to inconsistent results.

• Cell-based therapies
• Mesenchymal stromal cells (MSC)
• Osteonecrosis

Osteonecrosis of femoral head (ONFH) is a seriously degenerative disease with no effective therapies to slow its progression. Several studies have reported short-term efficacy of stem cells on early-stage ONFH. However, its long-term effect was still unclear especially on progression events. This study was performed to evaluate the long-term efficacy and safety of stem cells and analyze its optimal age group and cell number.

Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42020136094. Following PRISMA guideline, we searched 8 electronic databases on January 5, 2020, and rigorous random controlled trials (RCTs) utilizing stem cell therapy on early-stage ONFH were included. Quality and bias were analyzed. Pooled analysis was performed to assess difference between various outcomes.

A total of 13 RCTs (619 patients with 855 hips) were included. The application of stem cells significantly delayed collapse of femoral head(I², 70%; RR, 0.54; 95% CI, 0.33 to 0.89; P < .00001) and total hip replacement (THR) (I², 68%; RR, 0.55; 95% CI, 0.34 to 0.90; P = .02) in the long term. It effectively decreased the events of collapse of femoral head (≥ 60 months) (I², 0%; RR, 0.37; 95% CI, 0.28 to 0.49; P < .00001) and THR (> 36 months) (I², 0%; RR, 0.32; 95% CI, 0.23 to 0.44; P < .00001). There existed a beneficial effect for patients under 40 (Collapse of femoral head: I², 56%; RR, 0.41; 95% CI, 0.23 to 0.76; P = .004) (THR: I², 0%; RR, 0.31; 95% CI, 0.23 to 0.42; P < .00001). In addition, quantity of stem cells at 10⁸ magnitude had better effects on disease progression events (I², 0%; RR, 0.34; 95%CI, 0.16 to 0.74; P = .007). Besides, there were no significant differences on adverse events between the stem cell group and control group (I², 0%; RR, 0.82; 95% CI, 0.39 to 1.73; P = .60).

Our findings build solid evidence that stem cell therapy could be expected to have a long-term effect on preventing early-stage ONFH patients from progression events, such as collapse of femoral head and total hip replacement. Furthermore, patients under 40 may be an ideal age group and the optimal cell number could be at 10⁸ magnitude for this therapy. Further studies including strict RCTs are required to evaluate a clear effect of stem cells on ideal patient profile and the procedures of implantation.

• Collapse of femoral head
• Meta-analysis
• Osteonecrosis of femoral head
• Progression events
• Stem cells
• Total hip replacement

During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell–tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, β-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC‰ of MNC with 9.8 ± 10.7‰ for the TCP and 12.8 ± 10.2‰ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration.

• allograft
• bone defect
• bone remodeling
• ceramic filter
• surgical suction
• total joint arthroplasty
• β-TCP

• Aged
• Bone Regeneration
• Bone Substitutes/chemistry
• Cell Differentiation
• Cell Proliferation
• Ceramics/chemistry
• Female
• Humans
• Male
• Mesenchymal Stem Cells/cytology
• Osteoarthritis/pathology
• Osteoarthritis/surgery
• Suction
• Tissue Scaffolds/chemistry
• Vacuum

• Mesenchymal stromal cells
• Orthopedic surgery

• Adipose Tissue
• Animals
• Bone Marrow
• Bone Marrow Cells
• Bone Marrow Transplantation/methods
• Bone Marrow Transplantation/trends
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cell Transplantation/trends
• Mesenchymal Stem Cells/metabolism
• Musculoskeletal Diseases/physiopathology
• Musculoskeletal Diseases/therapy

Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, “light-bulb” procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (β-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH.

From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes.

The 5-years survival rate of using β-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative.

Our results suggest that “light-bulb” procedure grafting with β-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

• Beta-tricalcium phosphate
• Head-preserving surgery
• Osteonecrosis of the femoral head

• bone defect
• decalcified bone matrix
• individual tissue-engineered bones
• mesenchymal stem cells

• Cell functions
• Cell identity
• Cell therapy
• Mesenchymal stem/stromal cells

• Adipose Tissue/cytology
• Bone Marrow Cells/cytology
• Cell Differentiation
• Cell- and Tissue-Based Therapy
• Graft vs Host Disease/prevention & control
• Humans
• Immunosuppression Therapy
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Wnt Signaling Pathway

• 17k15729 Japan Society for the Promotion of Science
• Suzuken Memorial Foundation

• Affinity peptide
• Bone marrow-derived mesenchymal stem cell
• Osteonecrosis of the femoral head
• β-tricalcium phosphate

• MSC
• biologics
• musculoskeletal healing
• novel treatments
• tissue regeneration

To propose a new definition of the pericollapse stage of osteonecrosis of the femoral head (ONFH) and review its significance in disease diagnosis and treatment selection.

A search for eligible studies was conducted in three electronic databases including PubMed, Cochrane Library, and Embase up to August 10, 2018, using the following keywords: “osteonecrosis”, “prognosis”, and “treatment”.

Investigations appraising the clinical signs, symptoms, and imaging manifestations in different stages of ONFH were included. Articles evaluating the prognosis of various joint-preserving procedures were also reviewed.

The pericollapse stage refers to a continuous period in the development of ONFH from the occurrence of subchondral fracture to early collapse (<2 mm), possessing specific imaging features that mainly consist of bone marrow edema and joint effusion on magnetic resonance imaging (MRI), crescent signs on X-ray films, and clinical manifestations such as the sudden worsening of hip pain. Accumulating evidence has indicated that these findings may be secondary to the changes after subchondral fractures. Of note, computed tomography provides more information for identifying possible subchondral fractures than does MRI and serves as the most sensitive tool for grading the pericollapse lesion stage. The pericollapse stage may indicate a high possibility of progressive disease but also demonstrates satisfactory long- and medium-term outcomes for joint-preserving techniques. In fact, if the articular surface subsides more than 2 mm, total hip arthroplasty is preferable.

The pericollapse stage with distinct clinical and imaging characteristics provides a last good opportunity for the use of joint-preserving techniques. It is necessary to separate the pericollapse stage as an independent state in evaluating the natural progression of ONFH and selecting an appropriate treatment regimen.

• Joint-Preserving Procedure
• Osteonecrosis of the Femoral Head
• Pericollapse
• Prognosis

• bone marrow concentrate
• bone regeneration
• cell therapy
• mesenchymal stem cell
• osteogenesis

• Cell death
• Cell function
• Cell therapy
• Mesenchymal stem cell

• Aging
• Mesenchymal stem cells
• Regeneration
• Subpopulation
• Therapy

• Adult
• Aged
• Aging
• Animals
• Cell Differentiation
• Cell Proliferation
• Cellular Senescence
• Humans
• Mesenchymal Stem Cells/metabolism
• Mice
• Transcriptome/genetics
• Young Adult

• R01 DK074095 NIDDK NIH HHS
• R01-AG025016 NIH HHS
• R01 AG025016 NIA NIH HHS
• R01 EB005718 NIBIB NIH HHS
• R01-DK074095 NIH HHS
• R01-EB005718 NIH HHS

The last couple of decades have seen brilliant progress in stem cell therapies, including native, genetically modified, and engineered stem cells, for osteonecrosis of the femoral head (ONFH). In vitro studies evaluate the effect of endogenous or exogenous factor or gene regulation on osteogenic phenotype maintenance and/or differentiation towards osteogenic lineage. The preclinical and clinical outcomes accelerate the clinical translation. Bone marrow mesenchymal stem cells and adipose-derived stem cells have demonstrated better effects in the treatment of femoral head necrosis. Various materials have been used widely in the ONFH treatment in both preclinical and clinical trials. In a word, in vivo and multiscale efforts are expected to overcome obstacles in the approaches for treating ONFH and provide clinical relevance and commercial strategies in the future. Therefore, we will discuss the above aspects in this paper and present our opinions.

• Cell therapy
• Hip
• Mesenchymal stem cells
• Osteonecrosis

• Animals
• Exosomes/metabolism
• Femur Head Necrosis/therapy
• Humans
• Stem Cell Transplantation
• Stem Cells/cytology
• Translational Research, Biomedical
• Treatment Outcome

• National Natural Science Foundation of China

Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.

• avascular necrosis
• biomaterials
• bone defects
• fracture repair
• mechanical stimulation
• non-union
• stem cells
• tissue engineering

• Decompression, surgical
• Hip joint
• Operative procedures
• Osteonecrosis
• Stem cells

• Bone Transplantation
• Decompression, Surgical
• Femur Head
• Femur Head Necrosis/surgery
• Humans
• Male
• Middle Aged
• Treatment Outcome

• Avascular necrosis of femoral head
• Biological therapies
• Core decompression
• Hip
• Osteonecrosis
• Regenerative therapies

• Arthroplasty, Replacement, Hip/statistics & numerical data
• Biological Therapy/methods
• Decompression, Surgical/methods
• Femur Head Necrosis/mortality
• Femur Head Necrosis/therapy
• Hip Joint/surgery
• Humans
• Survival Analysis
• Survivorship
• Treatment Outcome

• Animals
• Femur Head/drug effects
• Femur Head/metabolism
• Femur Head Necrosis/chemically induced
• Femur Head Necrosis/drug therapy
• Femur Head Necrosis/etiology
• Femur Head Necrosis/metabolism
• Flavanones/therapeutic use
• Male
• PPAR gamma/analysis
• PPAR gamma/metabolism
• Protective Agents/therapeutic use
• Rabbits
• Receptors, Notch/analysis
• Receptors, Notch/metabolism
• Signal Transduction/drug effects
• Steroids/adverse effects
• Up-Regulation/drug effects

• Osteonecrosis of femoral head
• adiogenesis
• bone marrow mesenchymal stem cells
• glutathione
• osteogenesis
• reactive oxygen species

• ATMPs
• GMP
• bone tissue engineering
• cartilage tissue engineering
• mesenchymal stromal cells

• Avascular necrosis
• Hip
• Osteonecrosis
• Review

Age‐related (type‐II) osteoporosis is a common and debilitating condition driven in part by the loss of bone marrow (BM) mesenchymal stromal cells (MSC) and their osteoblast progeny, leading to reduced bone formation. Current pharmacological regiments targeting age‐related osteoporosis do not directly treat the disease by increasing bone formation, but instead use bisphosphonates to reduce bone resorption—a treatment designed for postmenopausal (type‐I) osteoporosis. Recently, the bone regenerative capacity of MSCs has been found within a very rare population of skeletal stem cells (SSCs) residing within the larger heterogeneous BM‐MSC pool. The osteoregenerative potential of SSCs would be an ideal candidate for cell‐based therapies to treat degenerative bone diseases such as osteoporosis. However, to date, clinical and translational studies attempting to improve bone formation through cell transplantation have used the larger, nonspecific, MSC pool. In this review, we will outline the physiological basis of age‐related osteoporosis, as well as discuss relevant preclinical studies that use exogenous MSC transplantation with the aim of treating osteoporosis in murine models. We will also discuss results from specific clinical trials aimed at treating other systemic bone diseases, and how the discovery of SSC could help realize the full regenerative potential of MSC therapy to increase bone formation. Finally, we will outline how ancillary clinical trials could be initiated to assess MSC/SSC‐mediated bone formation gains in existing and potentially unrelated clinical trials, setting the stage for a dedicated clinical investigation to treat age‐related osteoporosis. Stem Cells Translational Medicine2017;6:1930–1939

• Aging
• Ancillary clinical trials
• Cellular therapy
• Osteoporosis
• Stromal cells