Dataset Information

Laser-activated autologous adipose tissue-derived stromal vascular fraction restores spinal cord architecture and function in multiple sclerosis cat model.

ABSTRACT:

Background

Multiple sclerosis (MS) is the most frequent non-traumatic neurological debilitating disease among young adults with no cure. Over recent decades, efforts to treat neurodegenerative diseases have shifted to regenerative cell therapy. Adipose tissue-derived stromal vascular fraction (SVF) comprises a heterogeneous cell population, considered an easily accessible source of MSCs with therapeutic potential in autoimmune diseases. This study aimed to assess the regenerative capacity of low-level laser-activated SVF in an MS cat model.

Methods

Fifteen adult Persian cats were used in this study: Group I (control negative group, normal cats), Group II (EB-treated group, induced for MS by ethidium bromide (EB) intrathecal injection), and Group III (SVF co-treated group, induced for MS then treated with SVF on day 14 post-induction). The SVF was obtained after digesting the adipose tissue with collagenase type I and injecting it intrathecal through the foramen magnum.

Results

The results showed that the pelvic limb's weight-bearing locomotion activity was significantly (P ≤ 0.05) recovered in Group III, and the Basso, Beattie, and Bresnahan (BBB) scores of hindlimb locomotion were significantly higher in Group III (14 ± 0.44) than Group II (4 ± 0.31). The lesion's extent and intensity were reduced in the magnetic resonance imaging (MRI) of Group III. Besides, the same group showed a significant increase in the expression of neurotrophic factors: BDNF, SDF and NGF (0.61 ± 0.01, 0.51 ± 0.01 and 0.67 ± 0.01, respectively) compared with Group II (0.33 ± 0.01, 0.36 ± 0.006 and 0.2 ± 0.01, respectively). Furthermore, SVF co-treated group revealed a significant (P ≤ 0.05) increase in oligodendrocyte transcription factor (Olig2) and myelin basic protein (4 ± 0.35 and 6 ± 0.45, respectively) that was decreased in group II (1.8 ± 0.22 and 2.9 ± 0.20, respectively). Moreover, group III showed a significant (P ≤ 0.05) reduction in Bax and glial fibrillary acidic protein (4 ± 0.53 and 3.8 ± 0.52, respectively) as compared with group II (10.7 ± 0.49 and 8.7 ± 0.78, respectively). The transmission electron microscopy demonstrated regular more compact, and markedly (P ≤ 0.05) thicker myelin sheaths (mm) in Group III (0.3 ± 0.006) as compared with group II (0.1 ± 0.004). Based on our results, the SVF co-treated group revealed remyelination and regeneration capacity with a reduction in apoptosis and axonal degeneration.

Conclusion

SVF is considered an easy, valuable, and promising therapeutic approach for treating spinal cord injuries, particularly MS.

SUBMITTER: Farid MF

PROVIDER: S-EPMC9832640 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Laser-activated autologous adipose tissue-derived stromal vascular fraction restores spinal cord architecture and function in multiple sclerosis cat model.

Farid Mariam F MF Abouelela Yara S YS Yasin Noha A E NAE Al-Mokaddem Asmaa K AK Prince Abdelbary A Ibrahim Marwa A MA Rizk Hamdy H

Stem cell research & therapy 20230111 1

<h4>Background</h4>Multiple sclerosis (MS) is the most frequent non-traumatic neurological debilitating disease among young adults with no cure. Over recent decades, efforts to treat neurodegenerative diseases have shifted to regenerative cell therapy. Adipose tissue-derived stromal vascular fraction (SVF) comprises a heterogeneous cell population, considered an easily accessible source of MSCs with therapeutic potential in autoimmune diseases. This study aimed to assess the regenerative capacit ...[more]

PMID: 36627662

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Project description:: In patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement, bone substitutes are currently evaluated as alternatives for autologous bone. However, bone substitutes have only osteoconductive properties and lack osteoinductive potential. Therefore, this phase I study evaluated the potential additive effect on bone regeneration by the addition of freshly isolated, autologous but heterologous stromal vascular fraction (SVF), which is highly enriched with adipose stromal/stem cells when compared with native adipose tissue. From 10 patients, SVF was procured using automatic processing, seeded on either β-tricalcium phosphate (n = 5) or biphasic calcium phosphate carriers (n = 5), and used for MSFE in a one-step surgical procedure. Primary objectives were feasibility and safety. The secondary objective was efficacy, evaluated by using biopsies of the augmented area taken 6 months postoperatively, concomitant with dental implant placement. Biopsies were assessed for bone, graft, and osteoid volumes. No adverse effects were reported during the procedure or follow-up (≥3 years). Bone and osteoid percentages were higher in study biopsies (SVF supplemented) than in control biopsies (ceramic only on contralateral side), in particular in β-tricalcium phosphate-treated patients. Paired analysis on the six bilaterally treated patients revealed markedly higher bone and osteoid volumes using microcomputed tomography or histomorphometric evaluations, demonstrating an additive effect of SVF supplementation, independent of the bone substitute. This study demonstrated for the first time the feasibility, safety, and potential efficacy of SVF seeded on bone substitutes for MSFE, providing the first step toward a novel treatment concept that might offer broad potential for SVF-based regenerative medicine applications.SignificanceThis is the first-in-human study using freshly isolated, autologous adipose stem cell preparations (the stromal vascular fraction [SVF] of adipose tissue) applied in a one-step surgical procedure with calcium phosphate ceramics (CaP) to increase maxillary bone height for dental implantations. All 10 patients received CaP plus SVF on one side, whereas bilaterally treated patients (6 of 10) received CaP only on the opposite side. This allowed intrapatient evaluation of the potential added value of SVF supplementation, assessed in biopsies obtained after 6 months. Feasibility, safety, and potential efficacy of SVF for bone regeneration were demonstrated, showing high potential for this novel concept.

Project description:BackgroundCell-based therapy using adipose-derived mesenchymal stem cells (ADSCs) is a promising treatment strategy for neurogenic bladder (NB) associated with spinal cord injury (SCI). However, therapeutic efficacy is low because of inefficient cell delivery. Cell sheets improve the efficacy of cell transplantation. Therefore, this study was conducted to investigate the therapeutic efficacy of transplanting ADSC sheets into an SCI rat model and focused on the function and pathological changes of the bladder.MethodsADSC sheets were prepared from adipose tissue of Sprague-Dawley (SD) rats using temperature-responsive cell culture dishes. Adult female SD rats were subjected to SCI by transection at the T10 level and administered ADSC sheets or gelatin sponge (the control group). Four and 8 weeks later, in vivo cystometrograms were obtained for voiding function assessment. Rats were sacrificed and the expression of various markers was analyzed in spinal and bladder tissues.ResultsThe number of β-tubulin III-positive axons in the ADSC sheet transplantation group was higher than that in the control group. Conversely, expression of glial fibrillary acidic protein in the ADSC sheet transplantation group was lower than that in the control group. Cystometry showed impairment of the voiding function after SCI, which was improved after ADSC sheet transplantation with increased high-frequency oscillation activity. Furthermore, ADSC sheet transplantation prevented disruption of the bladder urothelium in SCI rats, thereby maintaining the intact barrier. Compared with fibrosis of the bladder wall in the control group, the ADSC sheet transplantation group had normal morphology of the bladder wall and reduced tissue fibrosis as shown by downregulation of type 1 collagen. ADSC sheet transplantation also resulted in strong upregulation of contractile smooth muscle cell (SMC) markers (α-smooth muscle actin and smoothelin) and downregulation of synthetic SMC markers (MYH10 and RBP1).ConclusionADSC sheet transplantation significantly improved voiding function recovery in rats after SCI. ADSC sheet transplantation is a promising cell delivery and treatment option for NB related to SCI.

Dataset Information

Laser-activated autologous adipose tissue-derived stromal vascular fraction restores spinal cord architecture and function in multiple sclerosis cat model.

Background

Methods

Results

Conclusion

Publications

Laser-activated autologous adipose tissue-derived stromal vascular fraction restores spinal cord architecture and function in multiple sclerosis cat model.

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