Mesenchymal stem cell therapy to promote limb transplant functional recovery

Fitzpatrick, Emilie; Dehart, J.; Brown, Tommy A.; Salgar, Shashikumar K.

doi:10.1002/micr.30068

Cited by 4 publications

(22 citation statements)

References 62 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To ensure adequate number of MSCs home lesion site we administered both locally and systemically. The MSC dose and frequency used in this study was consistent with our own previous report [ 40 ] where we performed hind limb transplants in rats that involved sciatic nerve transection and repair followed by the administration of MSCs. Also, our protocol was similar to Yang et al [ 41 ] where they studied dual regeneration of muscle and nerve by intravenous injection of human-amniotic fluid-derived mesenchymal stem cells (5 × 10 6 for 3 days daily following surgery) in a sciatic nerve injury model.…”

Section: Methodssupporting

confidence: 83%

“…Nerve transection and repair was done on the right hind limb, and the contralateral limb served as a non-transected (naïve) nerve control. Starting ≥1 week post-SNR or INR, animals received manual physiotherapy for the right hind limb (≤5 min, 1–2 times per week) as described previously [ 40 ]. Primary outcome measures were limb sensory and motor functions, and secondary outcome measures were gastrocnemius mass, flexion contractures, and nerve histology.…”

Section: Methodsmentioning

confidence: 99%

“…The general surgical techniques used for SNR and INR are described previously [ 40 , 42 , 43 ] and the specific procedures used in this study are as follows.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

“Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model” – Experimental research

Bingham

Kniery

Jorstad

et al. 2019

Annals of Medicine and Surgery

Self Cite

View full text Add to dashboard Cite

Background Optimizing nerve regeneration and mitigating muscle atrophy are the keys to successful outcomes in peripheral nerve damage. We investigated whether mesenchymal stem cell (MSC) therapy can improve limb function recovery in peripheral nerve damage. Materials and methods We used sciatic nerve transection/repair (SNR) and individual nerve transection/repair (INR; branches of sciatic nerve - tibial, peroneal, sural) models to study the effect of MSCs on proximal and distal peripheral nerve damages, respectively, in male Lewis rats. Syngeneic MSCs (5 × 10 6 ; passage≤6) or saline were administered locally and intravenously. Sensory/motor functions (SF/MF) of the limb were assessed. Results Rat MSCs (>90%) were CD29 + , CD90 + , CD34 − , CD31 − and multipotent. Total SF at two weeks post-SNR & INR with or without MSC therapy was ∼1.2 on a 0–3 grading scale (0 = No function; 3 = Normal); by 12 weeks it was 2.6–2.8 in all groups (n ≥ 9/group). MSCs accelerated SF onset. At eight weeks post-INR, sciatic function index (SFI), a measure of MF (0 = Normal; −100 = Nonfunctional) was −34 and −77 in MSC and vehicle groups, respectively (n ≥ 9); post-SNR it was −72 and −92 in MSC and vehicle groups, respectively. Long-term MF (24 weeks) was apparent in MSC treated INR (SFI -63) but not in SNR (SFI -100). Gastrocnemius muscle atrophy was significantly reduced (P < 0.05) in INR. Nerve histomorphometry revealed reduced axonal area (P < 0.01) but no difference in myelination (P > 0.05) in MSC treated INR compared to the naive contralateral nerve. Conclusion MSC therapy in peripheral nerve damage appears to improve nerve regeneration, mitigate flexion-contractures, and promote limb functional recovery.

show abstract

Section: Methodssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

“Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model” – Experimental research

Bingham

Kniery

Jorstad

et al. 2019

Annals of Medicine and Surgery

Self Cite

View full text Add to dashboard Cite

show abstract

“…The lethal side effect of immunosuppressants raises the threshold of hand, face, and skin transplantations, which do not involve life‐threatening conditions. Combined immunosuppressive agents or BMMSCs, ADMSCs, and other cell therapies have been reported to have immunomodulatory effects in various transplantation models and to even promote functional recovery in rodent animals (Adamson et al, ; Fitzpatrick, Dehart, Brown, & Salgar, ; Plock et al, ; Radu et al, ; Siemionow & Nasir, ; Song, Muramatsu, Kurokawa, & Taguchi, ). Recent studies have also reported that rat iMSCs and human iMSCs have the potential of anti‐inflammatory effects in animal models (Ko et al, ; Lian et al, ; Wang et al, ; Yang et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Scale bars: 50 μm. ADMSCs, adipose-derived MSCs; BMMSCs, bone marrow-derived MSCs; hAD, human ADMSCs; hBM, human BMMSCs; hiM, human iMSCs; MSCs, mesenchymal stem cells; iMSCs, iPSCsderived mesenchymal stem cells; iPSCs, induced pluripotent stem cells; rAD, rat ADMSCs; rBM, rat BMMSCs have immunomodulatory effects in various transplantation models and to even promote functional recovery in rodent animals (Adamson et al, 2007;Fitzpatrick, Dehart, Brown, & Salgar, 2017;Plock et al, 2015;Radu et al, 2016;Siemionow & Nasir, 2007;Song, Muramatsu, Kurokawa, & Taguchi, 2005). Recent studies have also reported that rat iMSCs and human iMSCs have the potential of anti-inflammatory effects in animal models (Ko et al, 2018;Lian et al, 2010;Wang et al, 2018;Yang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Induced pluripotent stem cell‐derived mesenchymal stem cells prolong hind limb survival in a rat vascularized composite allotransplantation model

et al. 2019

View full text Add to dashboard Cite

Background The reduction of systemic immunosuppressive agents is essential for the expansion of vascularized composite allotransplantation (VCA) in a clinical setting. The purpose of this study is to compare human‐induced pluripotent stem cell‐derived mesenchymal stem cells (iMSCs) with four other types of mesenchymal stem cells (human bone marrow‐derived MSCs [BMMSCs], human adipose‐derived MSCs [ADMSCs], rat BMMSCs, and rat ADMSCs) in vitro, and to investigate the in vivo immunomodulatory effect of iMSCs in a rat VCA model. Materials and methods One Brown Norway (BN) rat, 2 Lewis (LEW) rats, and 1 Wistar rat were used in the mixed lymphocyte reaction (MLR), and 9 BN rats and 3 LEW rats (for donors), and 24 LEW rats (for recipients) were used in the VCA model. The abovementioned five types of MSCs were imaged to examine their morphology and were also tested for suppressor function using a MLR. The 24 recipient LEW rats were divided randomly into four groups, and subjected to orthotopic hind limb transplantation. The three control groups were the Iso group, in which transplantation was performed on from three to six LEW rats without immunosuppressive treatment (n = 6); the FK group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus alone (FK 506, 0.2 mg/kg, days 0–6 postoperatively, intraperitoneally) (n = 6); and the UT group, in which transplantation was performed from BN rats to LEW rats without any immunosuppressive treatment (n = 6). The experimental group was the iMSC group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus (FK 506, 0.2 mg/kg, days 0–6 postoperatively, intraperitoneally) and injected with iMSCs (2 × 106 cells, day 7, intravenously) (n = 6). Hind limb survival was assessed by daily inspection of gross appearance until 50 days postoperatively. Histology of the skin and muscle biopsy were investigated on day 14 postoperatively. A time series of the plasma cytokine level (before transplantation, and at 10, 14, and 17 days after transplantation) was also analyzed. Results The size of adherent and trypsinized iMSCs was 67.5 ± 8.7 and 9.5 ± 1.1 μm, respectively, which was the smallest among the five types of MSCs (p < .01). The absorbance in MLR was significantly smaller with rat ADMSCs (p = .0001), human iMSCs (p = .0006), rat BMMSCs (p = .0014), human ADMSCs (p = .0039), and human BMMSCs (p = .1191) compared to without MSCs. In vivo, iMSC treatment prolonged hind limb survival up to 12.7 days in macroscopic appearance, which is significantly longer than that of the FK group (p < .01). Histology of the skin and muscle biopsy revealed that mononuclear cell infiltration was significantly reduced by iMSC injection (p < .01). iMSC treatment also affected proinflammatory cytokines (interferon‐gamma (IFNγ) and tumor necrosis factor α (TNFα)) and the anti‐inflammatory cytokine (interleukin‐10 (IL‐10)) of the recipient plasma. The IFNγ levels at Δ14 and the TNFα levels at Δ...

show abstract

Expression of RUNX2 and Osterix in Rat Mesenchymal Stem Cells during Culturing in Osteogenic-Conditioned Medium

et al. 2020

View full text Add to dashboard Cite

We studied the expression of transcription factors RUNX2 and Osterix after addition of a concentrate of osteogenic-conditioned medium to the culture medium for osteogenic differentiation of mesenchymal stem cells (MSC). The obtained concentrate of osteogenic-conditioned medium containing a complex of bioactive substances with a molecular weight >10 kDa provided MSC differentiation into osteoblasts, which was confirmed by high level of expression of transcription factors RUNX2 and Osterix in comparison with the negative control. The highest expression of transcription factor Osterix was revealed on day 14 of MSC culturing in the presence of osteogenic supplement StemPro (positive control) and the studied concentrate of osteogenic-conditioned medium.

show abstract

Mesenchymal stem cell therapy to promote limb transplant functional recovery

Abstract: Bone marrow-derived MSC therapy appears to improve sensory function recovery in a rat limb transplant model. Published 2016. This article is a U.S. Government work and is in the public domain in the USA Microsurgery 37:222-234, 2017.

Cited by 4 publications

References 62 publications

“Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model” – Experimental research

“Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model” – Experimental research

Induced pluripotent stem cell‐derived mesenchymal stem cells prolong hind limb survival in a rat vascularized composite allotransplantation model

Expression of RUNX2 and Osterix in Rat Mesenchymal Stem Cells during Culturing in Osteogenic-Conditioned Medium

Contact Info

Product

Resources

About