Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients

Abstract

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types—bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)—highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions.

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“…The field of bioengineering has to advance: Human autologous adipose-derived stem cells (ASCs) can more widely be used to obtain a scaffold-free 3D osteogenic structure transplanted for patients with intercalary defects after bone tumor resection [8]. Bone marrow mesenchymal stem cells (MSCs) can have a large impact in the promising field of bone regeneration and defect repair with and without biomaterials such as ceramic, biodegradable polymers, and composite materials [3].…”

“…Read this interesting instructional course lecture on a novel bone transport technique [16]. This review article discusses the tremendous progress being made with potential future applications in the field of bioengineering [3]. In this study, the authors report on their progress made with new developments in endoprosthetic replacement using a new design and material [13].…”

“…c This review article discusses the tremendous progress being made with potential future applications in the field of bioengineering [3].…”