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Lee HY, An SB, Hwang SY, Hwang GY, Lee HL, Park HJ, Shin J, Kim KN, Wee SW, Yoon SL, Ha Y. Synergistic enhancement of spinal fusion in preclinical models using low-dose rhBMP-2 and stromal vascular fraction in an injectable hydrogel composite. Mater Today Bio 2025; 30:101379. [PMID: 39759847 PMCID: PMC11699625 DOI: 10.1016/j.mtbio.2024.101379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/20/2024] [Accepted: 12/03/2024] [Indexed: 01/07/2025] Open
Abstract
Spinal fusion surgery remains a significant challenge due to limitations in current bone graft materials, particularly in terms of bioactivity, integration, and safety. This study presents an innovative approach using an injectable hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) hydrogel combined with stromal vascular fraction (SVF) and low-dose recombinant human BMP-2 (rhBMP-2) to enhance osteodifferentiation and angiogenesis. Through a series of in vitro studies and preclinical models involving rats and minipigs, we demonstrated that the hydrogel system enables the sustained release of rhBMP-2, resulting in significantly improved bone density and integration, alongside reduced inflammatory responses. The combination of rhBMP-2 and SVF in this injectable formulation yielded superior spinal fusion outcomes, with enhanced mechanical properties and increased bone mass in both small and large animal models. These findings suggest that this strategy offers a promising and safer alternative for spinal fusion, with strong potential for clinical application.
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Affiliation(s)
- Hye Yeong Lee
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Seong Bae An
- Department of Neurosurgery, School of Medicine, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea
- Graduate School, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Sae Yeon Hwang
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Gwang Yong Hwang
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Hye-Lan Lee
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Hyun Jung Park
- Department of Research Center, CGBio., co. Ltd, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Joongkyum Shin
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Keung Nyun Kim
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Sung Won Wee
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Sol Lip Yoon
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
| | - Yoon Ha
- Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea
- POSTECH Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of Korea
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Gareev I, Beylerli O, Ilyasova T, Ahmad A, Shi H, Chekhonin V. Therapeutic application of adipose-derived stromal vascular fraction in myocardial infarction. iScience 2024; 27:109791. [PMID: 38736548 PMCID: PMC11088339 DOI: 10.1016/j.isci.2024.109791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024] Open
Abstract
The insufficiency of natural regeneration processes in higher organisms, including humans, underlies myocardial infarction (MI), which is one of the main causes of disability and mortality in the population of developed countries. The solution to this problem lies in the field of revealing the mechanisms of regeneration and creating on this basis new technologies for stimulating endogenous regenerative processes or replacing lost parts of tissues and organs with transplanted cells. Of great interest is the use of the so-called stromal vascular fraction (SVF), derived from autologous adipose tissue. It is known that the main functions of SVF are angiogenetic, antiapoptotic, antifibrotic, immune regulation, anti-inflammatory, and trophic. This study presents data on the possibility of using SVF, targeted regulation of its properties and reparative potential, as well as the results of research studies on its use for the restoration of damaged ischemic tissue after MI.
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Affiliation(s)
- Ilgiz Gareev
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Ozal Beylerli
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Tatiana Ilyasova
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Aamir Ahmad
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Huaizhang Shi
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 1500, China
| | - Vladimir Chekhonin
- Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- The National Medical Research Center for Endocrinology, Moscow, Russian Federation
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Tantuway V, Thomas W, Parikh MB, Sharma R, Jeyaraman N, Jeyaraman M. Clinical Outcome of Minimally Manipulated, Mechanically Isolated Autologous Adipose Tissue-Derived Stromal Vascular Fraction (Sahaj Therapy®) in Knee Osteoarthritis-Randomized Controlled Trial. Indian J Orthop 2023; 57:1646-1658. [PMID: 37766954 PMCID: PMC10519910 DOI: 10.1007/s43465-023-00981-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023]
Abstract
Introduction Regenerative therapy has shown promising results in the treatment of osteoarthritis (OA) knee with Kellgren-Lawrence (KL) Grades I-III. We compared the safety, efficacy, functional, and clinical outcomes of intra-articular implantation of autologous adipose tissue-derived stromal vascular fraction (SVF) isolated using direct ultrasonic cavitation (Sahaj therapy-Cell Innovation Patented Technology) and saline injection in knee osteoarthritis. Materials and Methods The present prospective observational study was conducted over 3 years. We enrolled 120 patients in our study, where four patients got excluded as they did not meet the inclusion criteria. The remaining 116 patients were randomized into two groups, one with autologous adipose tissue-derived SVF and the other group with saline injection. A comparison of mean KOOS and VAS scores at different follow-ups was done using Paired 't' test. A p value of < 0.05 was considered significant. Results The results show that the SVF group had significantly higher KOOS scores (78.49 ± 6.54 in the SVF group vs 59.19 ± 5.14 in the saline group), respectively (p < 0.001). Similarly, the SVF group had significantly lesser VAS scores (3.17 ± 0.94 in the SVF group vs 3.89 ± 1.04 in the saline group), respectively (p < 0.001). Conclusions Autologous adipose tissue-derived SVF is a better choice for treating knee osteoarthritis. For individuals with degenerative osteoarthritis, autologous SVF grafting in the same surgical procedure is an innovative and promising treatment modality. Even after 3 years of follow-up, the study participants with OA knee have shown a good clinical and functional outcome.
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Affiliation(s)
- Vinay Tantuway
- Department of Orthopaedics & Traumatology, Index Medical College Hospital and Research Centre, Indore, Madhya Pradesh India
| | - Wayne Thomas
- Department of Tumor Immunology, The University of Newcastle, Callaghan, Australia
| | - Mittal B. Parikh
- Department of Orthopaedics, Navjivan Hospital, Ahmedabad, Gujarat India
| | - Raj Sharma
- Sahaj Regenerative Cell Therapeutics, Indore, Madhya Pradesh India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu India
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu India
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Sharma S, Muthu S, Jeyaraman M, Ranjan R, Jha SK. Translational products of adipose tissue-derived mesenchymal stem cells: Bench to bedside applications. World J Stem Cells 2021; 13:1360-1381. [PMID: 34786149 PMCID: PMC8567449 DOI: 10.4252/wjsc.v13.i10.1360] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/02/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With developments in the field of tissue engineering and regenerative medicine, the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians. Among all the available biological tissues, research and exploration of adipose tissue have become more robust. Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential. The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth, proliferation, and differentiation. Adipose tissue, apart from being the powerhouse of energy storage, also functions as the largest endocrine organ, with the release of various adipokines. The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues. The results of adipose-derived stem-cell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis, fat graft integration, and survival within the recipient tissue and promote the regeneration of tissue are promising. Adipose tissue gives rise to various by-products upon processing. This article highlights the significance and the usage of various adipose tissue by-products, their individual characteristics, and their clinical applications.
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Affiliation(s)
- Shilpa Sharma
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
| | - Sathish Muthu
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu 624304, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India.
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh 201306, India
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De Francesco F, Mannucci S, Conti G, Dai Prè E, Sbarbati A, Riccio M. A Non-Enzymatic Method to Obtain a Fat Tissue Derivative Highly Enriched in Adipose Stem Cells (ASCs) from Human Lipoaspirates: Preliminary Results. Int J Mol Sci 2018; 19:E2061. [PMID: 30011969 PMCID: PMC6073668 DOI: 10.3390/ijms19072061] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 07/07/2018] [Accepted: 07/11/2018] [Indexed: 12/14/2022] Open
Abstract
Adipose tissue possesses phenotypic gene expression characteristics that are similar to human mesenchymal stem cells (hMSCs). Nevertheless, the multilineage potential may be inhibited, and cells may not expand adequately to satisfy the requirements of Good Manufacturing Practice (cGMP). An autologous hMSC-enriched fat product would fulfil the void from a biomedical and clinical perspective. In this study, we suggest a novel mechanism using a closed system without enzymes, additives or other modifications, which will produce non-expanded, accessible material. This decentralized fat product, unlike unprocessed lipoaspirates, adequately encloses the vascular stroma with adipocytes and stromal stalks along with their vascular channels and lumina. This fat product contained hASCs and fewer hematopoietic elements such as lipoaspirates, which were digested enzymatically according to flow cytometric investigations, and molecular analysis also showed significant hASC uniformity within the cells of the stromal vascular tissue. Moreover, the fat product produced a higher quantity of hASCs similar to hMSCs in isolation with the typical characteristics of an osteogenic, chondrogenic and adipogenic lineage. Interestingly, these properties were evident in the non-enzymatic derived adipose tissue, as opposed to hASCs in isolation from the enzymatically digested lipoaspirates, suggesting that the aforementioned procedure may be an adequate alternative to regenerate and engineer tissue for the treatment of various medical conditions and promote efficient patient recovery.
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Affiliation(s)
- Francesco De Francesco
- Department of Reconstructive Surgery and Hand Surgery (SOD Chirurgia Ricostruttiva e Chirurgia della Mano), AOU "Ospedali Riuniti", via Conca, 60126 Ancona, Italy.
| | - Silvia Mannucci
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37134 Verona, Italy.
| | - Giamaica Conti
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37134 Verona, Italy.
| | - Elena Dai Prè
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37134 Verona, Italy.
| | - Andrea Sbarbati
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37134 Verona, Italy.
| | - Michele Riccio
- Department of Reconstructive Surgery and Hand Surgery (SOD Chirurgia Ricostruttiva e Chirurgia della Mano), AOU "Ospedali Riuniti", via Conca, 60126 Ancona, Italy.
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