Delivery of Mesenchymal Stem Cells in Biomimetic Engineered Scaffolds Promotes Healing of Diabetic Ulcers

Assi, Roland; Foster, Trenton R.; He, Hao; Stamati, Katerina; Bai, Hualong; Huang, Yingqun; Hyder, Fahmeed; Rothman, Douglas L.; Shu, Chang; Homer‐Vanniasinkam, Shervanthi; Cheema, Umber; Dardik, Alan

doi:10.2217/rme-2015-0045

Cited by 59 publications

(58 citation statements)

References 41 publications

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“…Hence, the notion of implanting stem cells pre-or postdifferentiated to a neural lineage may be working at cross-purposes to the developmental imperatives of the multipotent cells in certain cases, particularly for systemic repair of complex organs such as the spinal cord and brain (25,32,33). Our results suggest that scaffolded hMSCs may be adaptable for implantation directly into the contused spinal cord of patients in the subacute phase after injury when autoimmune and inflammatory insults peak (4,33,41,48).…”

Section: Discussionmentioning

confidence: 86%

“…Although activation by donor hMSCs of endogenous NSC proliferation, migration, and differentiation was previously described in the brain (36), the significant difference between the rats treated with scaffolded and nonscaffolded hMSCs suggests that a synthetic matrix tailored to enhance hMSC survival and stemness potently augmented the location-specific impact of hMSCs on adult spinal cord neurogenesis post-SCI, providing therapeutic benefits (9, 39). We also examined whether intraparenchymal angiogenesis, an important primary tissue repair mechanism that can be induced by MSCs (41), was promoted by the scaffolded hMSC implant around the epicenter; a nearly fourfold increase in group mean IR against laminin, a primary angiogenic marker (41), was detected by L9393, a pan antilaminin antibody, in the treated spinal cords relative to the controls (P < 0.05; Fig. 5E).…”

Section: Neurobiological Mechanisms Underlying Post-sci Recovery Follmentioning

confidence: 99%

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Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Ropper

Thakor

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.spinal cord injury | recovery neurobiology | mesenchymal stromal stem cell | PLGA | locomotion R epair of neurotrauma, stroke, and neurodegenerative diseases remains an unmet medical demand because of their pathophysiological complexity and the limited spontaneous healing capacity of adult mammalian CNS. Human mesenchymal stromal stem cells (hMSCs) offer autologous transplantation feasibility (1-4) and have been studied both experimentally and clinically for traumatic brain injury (TBI) and spinal cord injury (SCI) (5-8). Although MSCs possess homeostatic and proneurogenic activities (7, 9), studies relying on neural transdifferentiation (i.e., putative differentiations of MSCs into neural cells without reentering the pluripotency phase) did not show long-term functional improvement in SCI models. The poor outcomes were attributed mainly to suboptimal survival of MSCs, leaving key therapeutic mechanisms undetermined (10). We previously established a 3D cell delivery technology by seeding neural stem cells (NSCs) in biodegradable polymer scaffolds that significantly improved donor efficacy and enabled investigation of NSC repair mechanisms in t...

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Section: Discussionmentioning

confidence: 86%

Section: Neurobiological Mechanisms Underlying Post-sci Recovery Follmentioning

confidence: 99%

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Ropper

Thakor

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…In a recent study, MSCs in a collagen matrix were used to assess the progression of DFU healing in a murine model. The conclusions were satisfactory, with greater healing found in mice treated with MSCs compared to the control mice [94].…”

Section: Stem Cellsmentioning

confidence: 82%

Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments

et al. 2019

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Diabetic foot ulcers (DFUs) are very important diabetes-related lesions that can lead to serious physical consequences like amputations of limbs and equally severe social, psychological, and economic outcomes. It is reported that up to 25% of patients with diabetes develop a DFU in their lifetime, and more than half of them become infected. Therefore, it is essential to manage infection and ulcer recovery to prevent negatives outcomes. The available information plays a significant role in keeping both physicians and patients aware of the emerging therapies against DFUs. The purpose of this review is to compile the currently available approaches in the managing and treatment of DFUs, including molecular and regenerative medicine, antimicrobial and energy-based therapies, and the use of plant extracts, antimicrobial peptides, growth factors, ozone, devices, and nano-medicine, to offer an overview of the assessment of this condition.2 of 32 history [2]. DFUs are one of the most severe complications of diabetes, and more than half of those ulcers become infected. Every single one of these infected lesions has the potential to get worse and compromise the integrity of the lower limbs. To avoid amputations and improve the patient's quality of life, it is very important to implement a strict program for the prevention and treatment of ulcers, as well as proper management of infections [3]. Thus, it is critical to keep diabetes patients aware of new therapies and treatments and their availability in the healthcare system. The treatment of DFUs requires a multidisciplinary approach with proper medical tools, skills, and knowledge. This starts from patient education, with the application of new classifications to guide the treatment to prevent amputations. New diagnosis methods should become available, such as the 16S ribosomal DNA sequence in bacteria, to provide a better understanding of the microbiota in DFUs. It is reported that DFU has a polymicrobial nature, and, according to its geographical location, certain marked differences, wound characteristics, antibiograms according to local epidemiology, individualized antimicrobial guided therapy, regular debridement, regular assessment of wounds, and change of dressings. The latter characteristics are also aided by new biological and molecular therapies that were proven to improve infection control, the regulation of the local inflammatory profile, and improved quality of the cicatrizing process. In the next sections, this review presents an approach for the diagnosis and treatment of DFUs, focusing on the current advances in antimicrobial therapies, such as dressings,

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“…Promoting vascularization in collagen scaffold. 48 Alginate Gel Human BMSCs BMSCs seeded in calcium alginate gel that acts as immobilization matrices for the cells. Alginate gel-seeded BMSCs conditioned medium had quantifiable concentration of bFGF and VEGF as angiogenic factors.…”

Section: Lamininmentioning

confidence: 99%

A review on different methods to increase the efficiency of mesenchymal stem cell‐based wound therapy

Shojaei

Rahmati

Dehkordi

2019

Wound Repair Regeneration

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Mesenchymal stem cells (MSCs) accelerate wound healing but the harsh environment of wound site limits the engraftment, retention, and survival rate of transplanted cells. There are multiple approaches that amplify the therapeutic potential of MSCs. The MSCs derived from medical waste material, provide comparable regenerative abilities compared to traditional sources. The application of different scaffolds increases MSC delivery and migration into the wound. The spheroid culture of MSC increases the paracrine effects of the entrapped cells and the secretion of pro‐angiogenic and anti‐inflammatory cytokines. The MSC pretreating and preconditioning enhances the cell migration, proliferation, and survival rate, which lead to higher angiogenesis, re‐epithelialization, wound closure, and granulation tissue formation. Moreover, genetic modification has been performed in order to increase MSC angiogenesis, differentiation potential, as well as the cell life span. Herein, we review the results of aforementioned approaches and provide information accommodating to the continued development of MSC‐based wound therapy in the future.

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Delivery of Mesenchymal Stem Cells in Biomimetic Engineered Scaffolds Promotes Healing of Diabetic Ulcers

Cited by 59 publications

References 41 publications

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments

A review on different methods to increase the efficiency of mesenchymal stem cell‐based wound therapy

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