Abstract
Purpose: We investigated the use of human Cord Lining Mesenchymal Stem Cells (CL-MSCs) (US Patent number 9,737,568), in a rabbit hindlimb ischemia model, and evaluated their potential in stimulating neovascularization. Allogenic human CL- MSCs could potentially be used to treat patients with lower limb ischemia and non-healing wounds.Methods: Twenty rabbits were divided into two separate groups. We created a hindlimb ischemia model surgically. At 21 and 49 days post-operatively, animals in the treatment group were injected with CL-MSCs (500,000 cells per 0.2 ml on each site) at 10 different sites (Quadriceps- 4 sites, Hamstrings- 4 sites and Calf-−2 sites) in the hindlimb muscles. The control group received only saline injection to the corresponding sites at the same time point as the treatment group. We then evaluated the effects of treatment on neovascularization by angiography, laser doppler perfusion imaging, as well as by histology. We evaluated the tissue samples for any signs of local immune reaction to the cell implantation. We also observed the rabbit clinically for any adverse effects after treatment.Results: We found a higher number of CD31 positive cells in the treatment group, with a greater number of capillaries found in the treated muscles. The Rectus Femoris demonstrated a median vessel count/muscle fiber of 0.121 for the treatment group, compared to 0.076 in the control group (median difference 0.04; 95% CI 0.001–0.11; p = 0.041). The Gastrocnemius demonstrated a median vessel count/muscle fiber of 0.175 for the treatment group, compared to 0.089 in the control group (median difference 0.087; 95% CI −0.006 to 0.234; p = 0.07). Blood perfusion quantification through Laser Doppler Perfusion Imaging (LDPI) also demonstrated a non-statistically significant increase in perfusion in favor of the treatment group. CL-MSCs demonstrated no toxicity associated morbidity and minimal local immune reaction to implantation.Conclusion: CL-MSCs have a positive effect on angiogenesis in a rabbit hindlimb ischemia model. This preliminary data is encouraging and paves the way for future large animal studies or for clinical trials.
Highlights
Critical limb ischemia (CLI) is regarded as one of the most detrimental forms of peripheral artery disease with high rates of disability and mortality (Tu et al, 2015; Shishehbor et al, 2016; Teraa et al, 2016)
To overcome the pre-existing difficulties in the translational use of stem cells, we will be using a novel source of MSCs derived from human cord lining (US Patent number 9,737,568). We demonstrated that these Cord Lining Mesenchymal Stem Cells (CL-MSCs), when compared with MSCs derived from other gestational tissues; namely umbilical cord blood (CB-MSCs), placenta (PMSCs), and Wharton’s jelly (WJ-MSCs); have showed the highest proliferation and migration rate as well as prolongation in survival, which is attributed to their ability to dampen TH1 and TH2 responses (Stubbendorff et al, 2013)
The CL-MSCs are superior cells, with the most promising potential for cell based therapy because of their higher proliferative capacity, lower immunogeneity, and stronger immunosuppressive potential. This cGMP grade CLMSCs or CorLiCyte has been approved by US-Food and Drug Administration (FDA) for Phase1 clinical trial for non-healing diabetic wounds and is believed to be a promising alternative source of stem cells
Summary
Critical limb ischemia (CLI) is regarded as one of the most detrimental forms of peripheral artery disease with high rates of disability and mortality (Tu et al, 2015; Shishehbor et al, 2016; Teraa et al, 2016). CLI has affected more than 200 million people worldwide, with lower-middle income countries accounting for an increase in prevalence rate of 29%, and higher income countries reflecting a 13% increase (Fowkes et al, 2013; Sampson et al, 2014; Jelani et al, 2018) This was closely associated with a 1-year major amputation rate of 40% (Ryu et al, 2012; Ponemone et al, 2017), while mortality rates increased by 20% within 6 months of diagnosis and 50% after 5 years of diagnosis (Norgren et al, 2007; Teraa et al, 2016). Postoperative arterial re-occlusion is a rapid occurrence which further limits the intervention, and leaves CLI patients with no ideal alternatives for intervention (Lawall et al, 2011)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
