Application of Adipose-Derived Stem Cells in Bone Tissue Engineering: Current Status and Future Prospects Volume 63- Issue 2

Junming Zhang^1,2,3, Dawei Zhang² and Jiang Peng³*

• ¹Jinzhou Medical University, Jinzhou City, Liaoning Province, 121000, China
• ²Department of Orthopedics, 960 Hospital of PLA Jinan City, Shandong province, 250031, China
• ³Institute of Orthopedics, the Fourth Medical Center, Chinese PLA General Hospital, Beijing 100853, China

Received: September 05, 2025; Published: September 23, 2025

*Corresponding author: Jiang Peng, Institute of Orthopedics, the Fourth Medical Center, Chinese PLA General Hospital, Beijing 100853, China

DOI: 10.26717/BJSTR.2025.63.009876

Abstract PDF

ADSCs have garnered increasing attention in the field of bone tissue engineering due to their abundant sources, good proliferation capacity, and multi-directional differentiation potential. With the development of regenerative medicine, ADSCs have emerged as an ideal cell source, demonstrating significant application potential in bone repair and regeneration. Existing studies indicate that ADSCs can not only differentiate into osteoblasts and promote the formation of bone matrix but also enhance tissue regeneration by secreting growth factors and extracellular matrix components. However, ADSCs still face several challenges in clinical applications, such as low cell survival rates, unstable differentiation capabilities, and immune rejection issues. This article aims to review the current applications of ADSCs in bone tissue engineering, explore their mechanisms, advantages, and challenges in the bone repair process, and provide insights into future research directions by analyzing the latest research findings, thereby offering a theoretical basis for promoting the clinical application of ADSCs in bone tissue engineering.

Keywords: Adipose-Derived Stem Cells; Bone Tissue Engineering; Bone Repair; Cell Therapy; Regenerative Medicine

Abbreviations: ADSCs: Adipose-Derived Stem Cells; BTE: Bone Tissue Engineering; PLA: Polylactic Acid; HA: Hydroxyapatite; BMP: Bone Morphogenetic Proteins; ECM: Extracellular Matrix; EVs: Extracellular Vesicles; BMSCs: Bone Marrow-Derived Stem Cells; MSCs: Mesenchymal Stem Cells; DPSCs: Dental Pulp Stem Cells; DPN: Diabetic Peripheral Neuropathy; SLT: Selective Laser Trabeculoplasty

Adipose-Derived Stem Cells (ADSCs) have become a research hotspot in recent years due to their excellent immune regulation, tissue regeneration, and multipotent differentiation capabilities, attracting widespread attention [1]. Research shows that ADSCs can not only differentiate into adipocytes but also transform into various cell types such as osteoblasts and chondrocytes, which demonstrates their broad application potential in regenerative medicine. Bone Tissue Engineering (BTE) is an emerging interdisciplinary field aimed at repairing or regenerating damaged bone tissue through the combination of biomaterials, cells, and growth factors. The key to BTE lies in constructing scaffold materials that can support cell growth, differentiation, and new bone formation, while also promoting vascularization to ensure the successful regeneration of bone tissue [2]. In clinical practice, the repair of bone defects has always been a challenge. Traditional treatment methods such as autologous bone grafting have issues like donor site injury and insufficient bone quantity at the donor site. Therefore, it is particularly important to develop new strategies for bone tissue engineering. The application background and research progress of ADSCs in bone tissue engineering are continuously enriching. Recent studies have shown that ADSCs can undergo osteogenic differentiation on suitable biomaterial scaffolds, promoting bone regeneration.

By combining with various biomaterials, ADSCs not only enhance the regenerative capacity of bone defect sites but also improve the speed and quality of bone healing [3]. For example, using composite scaffolds such as polylactic acid (PLA) and hydroxyapatite (HA), researchers found that ADSCs can effectively promote bone mineralization and the expression of osteogenesis-related genes, thereby accelerating the bone regeneration process [4]. In summary, ADSCs, as an excellent source of stem cells, show broad application prospects in bone tissue engineering. Future research will further explore the interaction mechanisms of ADSCs with different biomaterials and how to optimize their application effects in bone regeneration, to promote their translational application in clinical treatment.

Characteristics of Adipose-Derived Stem Cells

Biological Characteristics and Proliferation Ability: ADSCs possess significant biological characteristics, including self-renewal ability and multipotent differentiation capacity. Research shows that ADSCs can rapidly proliferate in vitro while maintaining their stem cell properties. Specifically, ADSCs can undergo multiple cell divisions under suitable culture conditions without losing their differentiation potential, which gives them important application value in tissue repair and regeneration [5]. In addition, the cell surface markers of ADSCs, such as CD73, CD90, and CD105, indicate that they belong to the category of mesenchymal stem cells, possessing good multipotent differentiation ability, capable of differentiating into various cell types such as adipocytes, chondrocytes, and osteocytes [6]. By adjusting the composition of the culture medium and the addition of growth factors, ADSCs can be effectively induced to differentiate into specific cell types. For example, the addition of specific growth factors can promote their differentiation into osteoblasts, thereby playing a role in bone defect repair [7]. This multidirectional differentiation potential allows ADSCs to demonstrate significant application value in fields such as tissue engineering, regenerative medicine, and disease treatment.

Mechanisms of ADSCs in Bone Tissue Engineering

Signaling Pathways that Promote Bone Formation: ADSCs play an important role in bone tissue engineering, and their mechanism of promoting osteogenesis mainly involves the regulation of various signaling pathways. Research shows that signaling pathways such as Wnt/β-catenin, bone morphogenetic proteins (BMP), and transforming growth factor β (TGF-β) play a key role in the differentiation of ADSCs into osteoblasts. The Wnt signaling pathway promotes osteogenesis by regulating the stability of intracellular β-catenin, activating the expression of osteogenesis-related genes such as Runx2 and Osterix [8]. In addition, the BMP signaling pathway regulates the proliferation and differentiation of osteoblasts by activating Smad proteins, enhancing bone formation capacity [9]. The TGF-β signaling pathway also plays an important role in regulating the interaction between osteoblasts and osteoclasts. The interaction of these signaling pathways forms a complex signaling network that ensures the normal generation and repair of bone tissue [10,11].

The Role of Extracellular Matrix: Extracellular matrix (ECM) not only provides a supportive structure in bone tissue engineering but also influences the behavior of ADSCs through its components and physical properties. Major components of ECM, such as collagen, glycosaminoglycans, and proteoglycans, can regulate cell adhesion, proliferation, and differentiation by interacting with cell surface receptors [12,13]. For example, research has found that the osteogenic differentiation ability of ADSCs is significantly enhanced when cultured on a collagen-rich matrix, which is closely related to the mechanical properties of collagen and its activation of cellular signaling pathways [14]. In addition, extracellular vesicles (EVs), as an important component of the ECM, can further regulate the osteogenic process of ADSCs and promote bone regeneration by transporting bioactive molecules such as miRNAs and proteins [15,16].

Immune Regulatory Function: The immunomodulatory function of ADSCs cannot be ignored in bone tissue engineering. ADSCs can create a favorable microenvironment for bone tissue regeneration by secreting various cytokines and bioactive molecules to regulate local immune responses and reduce inflammation [17]. Research shows that ADSCs can inhibit the proliferation and activation of T cells, reducing the release of inflammatory mediators, which is crucial for the healing of bone defects [18]. In addition, ADSCs can promote the formation of M2 macrophages by regulating the polarization state of macrophages, thereby accelerating tissue repair and regeneration [19]. This immune regulatory mechanism provides a new perspective on the application of ADSCs in bone tissue engineering, indicating that they are not only a source of cells but also key regulatory factors that promote bone regeneration.

Comparison of ADSCs with Other Stem Cells

Comparison of BMSCs and ADSCs: Bone marrow-derived stem cells (BMSCs) and ADSCs are two commonly used types of mesenchymal stem cells (MSCs) with significant potential applications in regenerative medicine. The acquisition of ADSCs is relatively simple and non-invasive, sourced from adipose tissue, and they possess good proliferation capacity and multi-directional differentiation potential. In contrast, obtaining BMSCs requires invasive surgery, and their quantity is relatively limited, with a complex process for isolation and culture. Research has shown that ADSCs exhibit stronger advantages in immune regulation, anti-inflammation, and promoting angiogenesis. For example, in one study, ADSCs were found to demonstrate better anti-inflammatory capabilities than BMSCs in combating oxidative low-density lipoprotein-induced inflammation [20]. In addition, the clinical application of ADSCs in the treatment of osteoarthritis, cardiovascular diseases, and diabetes has also shown good results [21]. Although BMSCs still play an important role in certain specific situations, such as bone tissue regeneration, ADSCs have gradually become a research focus in regenerative medicine due to their ease of acquisition and superior biological properties.

Advantages and DPSCs: Dental pulp stem cells (DPSCs) are stem cells isolated from dental pulp tissue, possessing good proliferation ability and multi-directional differentiation potential. Compared to ADSCs and BMSCs, DPSCs exhibit unique advantages in tooth regeneration and repair. Research shows that DPSCs have good potential in forming dentin and tooth-related tissues, effectively promoting tooth regeneration [22]. However, the clinical application of DPSCs still faces some challenges, including the complexity of cell acquisition and culture processes, as well as functional inconsistencies that may arise from biological differences between individuals [23]. In addition, the research on DPSCs is relatively new, and the evidence for clinical applications is still insufficient, requiring further exploration of their potential in other tissue regeneration. Therefore, although DPSCs have significant advantages in dental regeneration, more research and validation are needed for their broader clinical applications.

The Clinical Significance of Selecting Appropriate Sources of Stem Cells: In regenerative medicine, selecting the appropriate source of stem cells is crucial for treatment effectiveness. Stem cells from different sources have distinct biological characteristics and clinical application potential. For example, ADSCs are widely used in the treatment of various diseases, such as osteoarthritis and cardiovascular diseases, due to their ease of acquisition and lower immunogenicity [24]. BMSCs have shown good effects in bone tissue regeneration and repair, but their acquisition process is relatively complex and may be accompanied by certain complications [25]. In addition, DPSCs have unique advantages in tooth regeneration, but their clinical application still needs further exploration. Therefore, when selecting the source of stem cells, specific clinical needs, cell characteristics, and the patient’s specific situation should be considered to achieve the best therapeutic effect. Future research should further explore the comparison and selection criteria between different sources of stem cells to promote the development of regenerative medicine.

Clinical Applications and Research Progress

Review of Existing Clinical Trials: By reviewing existing clinical trials, we can better understand the current trends and challenges in research. For example, clinical trials targeting diabetic peripheral neuropathy (DPN) show that despite a large number of registered and published studies, there is still a lack of comprehensive summaries, making it difficult to unify the evaluation of research directions and outcomes [26].

Success Cases and Application Effects: Successful clinical application cases not only demonstrate the effectiveness of new therapies but also lay the foundation for future research. For example, the application of selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma shows its superiority and safety in lowering intraocular pressure, making it one of the standards in clinical treatment [27]. In addition, the application of nanofat grafting technology in plastic surgery is gradually being widely accepted due to its positive effects on skin regeneration and repair, especially in the treatment of scars and chronic wounds [28]. These successful cases not only demonstrate the clinical effects of new technologies but also inspire ways to optimize treatment plans to improve patients’ quality of life.

Challenges and Future Directions

Maintaining Cell Survival and Function: Maintaining cell survival and function is a significant challenge in biomedical research, especially in the context of aging and related diseases. As age increases, the autophagic function of cells declines, which directly affects their metabolism and survival capacity. Studies have shown that autophagy is not only a mechanism for clearing cellular waste but is also closely related to cellular energy metabolism. For example, there is an important link between the maintenance of NAD and the effective recycling of mitochondrial function. This connection reveals the survival mechanisms of cells under stress, suggesting that we can enhance cell survival and function by regulating autophagy-related pathways, thereby providing new therapeutic targets for various aging-related diseases [29]. In addition, the research found that small non-coding RNAs (such as miRNAs) play an important regulatory role in cell survival, especially under oxidative stress conditions, which provides new directions for future intervention strategies [30]. Therefore, exploring the mechanisms of cell survival and functional maintenance not only helps to understand the process of cellular aging but also provides a theoretical basis for developing new therapeutic methods.

Ethical Issues and Regulatory Restrictions: In biomedical research, ethical issues and regulatory restrictions have always been important considerations. With the development of gene editing technologies such as CRISPR/Cas9, ethical controversies surrounding human genome editing have garnered increasing attention. The National Academy of Sciences and the National Academy of Medicine in the United States established an international committee to review the ethics and regulations of human genome editing, suggesting that experimental germline gene editing should be conducted under a strict ethical and regulatory framework to avoid potential negative impacts on individuals with defects [31]. In addition, research involving dementia patients also faces ethical challenges, particularly in obtaining informed consent and protecting participants’ rights [32]. Therefore, future research needs to find a balance between respecting individual rights and scientific progress, ensuring ethical compliance in research while promoting sustainable scientific development.

ADSCs have shown significant application potential and advantages in bone tissue engineering.

Currently, ADSCs still face numerous challenges in clinical applications, including variability in cell function, survival rates after transplantation, and integration capabilities. These factors may affect the effectiveness of bone healing and the prognosis of patients. Therefore, future research should focus on optimizing the in vitro culture and induction conditions of ADSCs, exploring their synergistic effects with biomaterials, and assessing the applicability of ADSCs from different sources and with different characteristics in bone tissue engineering. Additionally, in-depth studies on the behavior of ADSCs in the in vivo microenvironment, as well as the mechanisms of their migration, proliferation, and differentiation, may provide new insights for enhancing their clinical application outcomes.

ADSCs have broad prospects in the fields of regenerative medicine and bone repair. With the deepening of basic research and advancements in technology, ADSCs may play an increasingly important role in bone tissue engineering, promoting the development of personalized treatment and precision medicine. By continuously integrating multidisciplinary research findings and balancing different perspectives and discoveries, we hope to provide more effective treatment options for patients with bone injuries and defects, ultimately achieving the ideal goals of regenerative medicine.

National Key Research and Development Program: 2024YFA110860

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