Stem cell therapy for fracture non-union: The current evidence from human studies

Abstract

Non-union is a taxing complication of fracture management for both the patient and their surgeon. Modern fracture fixation techniques have been developed to optimise the biomechanical environment for fracture healing but do not guarantee union. Patient biology has a critical role in achieving union and stem cell therapy has potential for improving fracture healing at a cellular level to treat or avoid non-union. This article reviews the current understanding of non-union, concepts in bone healing and the current literature on the application of stem cells in non-union.

Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration

“…Mesenchymal stem/progenitor cells possess a high potential of tissue regeneration by proliferating and differentiating into cells constituting the tissue. Although tremendous efforts are being made by researchers and clinicians, there have been no established stem cell therapies for bone fracture to date, possibly due to difficulties in manipulating these cells [ 5 , 12 , 13 ]. We hypothesized that the mobilization of endogenous stem cells would be another mode of stem cell therapy.…”

“…Currently, stem cell therapy has garnered the attention of clinicians, and many clinical studies are underway. Such therapies are expected to improve the treatment outcomes but there are also drawbacks such as the accumulation of stem cells in the lung after intravenous injection, immune responses against allogenic stem cells, low rate of cell viability, oncological complications, and a need for special devices for cell expansion [ 5 , 12 , 13 ]. The employment of endogenous stem cells would be another option for treating bone fractures.…”

Delayed Union and Nonunion: Current Concepts, Prevention, and Correction: A Review

“…In another case series evaluating a combination therapy using autologous stomal cells loaded on collagen microspheres and delivered via platelet-rich plasma clots, rapid and effective bone union was seen following both tibial and femoral applications of the novel therapeutic [ 136 ]. However, the clinical efficacy of stem cell therapy in nonunion cases remains questionable, with no consensus as to the source, dosage, processing, or delivery of cells [ 132 , 133 , 134 ]. Current research exploring the paracrine effects of cell therapy and evaluating the efficacy of MSC exosome implantation aims to further refine the therapeutic use, and further development of cell therapy for clinical use is ongoing [ 132 , 137 ].…”

Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors

“…The approximate costs for treatment of long-bone non-unions are estimated to be at least USD 11,333 in the US [12], USD 17,000-18,000 in the UK [24], USD 9641 in Australia [25] and between USD 2900 and USD 6300 in Germany [16]. In the USA, a tibial shaft non-union was USD 13,870 more expensive than the regular healing process [26], while overall costs of delayed fracture healing in the USA are estimated at around USD 14.6 million annually [15].…”

“…As an elegant approach to accelerate fracture healing, stem cell therapy has been suggested, with the iliac crest being the most common and safest source of cells [117]. More locally, intramedullary reamer-irrigator aspirations (RIA), especially in the long tibia and femur bones, represent easy and reliable sources of stem cells [25,118,119]. Interestingly, without attempts to concentrate the number of colony-forming units, the number of real MSCs among hematopoietic progenitors and stromal cells may be low.…”