Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Meyerrose, Todd E.; Olson, Scott D.; Pontow, Suzanne; Kalomoiris, Stefanos; Jung, Yunjoon; Annett, Geralyn; Bauer, Gerhard; Nolta, Jan A.

doi:10.1016/j.addr.2010.09.013

Cited by 157 publications

(120 citation statements)

References 79 publications

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“…These cells are characterized for: 1) their adherence to plastic in standard culture conditions; positive expression for specific markers like CD73, CD90, CD105 and negative expression for hematopoietic markers like CD34, CD45, HLA-DR, CD14 or CD11B, CD79α or CD19 and 2) in vitro differentiation into at least osteoblasts, adipocytes and chondroblasts [3]. In recent years it has been increasingly accepted that their regenerative effects are mainly mediated by their secretome [4][5][6]. The secretome, which comprises the proteins released by cells, tissues or organisms, has been shown to be crucial to the regulation of different cell processes [7].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations

et al. 2013

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It has been previously shown that the secretome of Human Umbilical Cord Perivascular Cells (HUCPVCs), known for their mesenchymal like stem cell character, is able to increase the metabolic viability and hippocampal neuronal cell densities. However, due to the different micro-environments of the distinct brain regions it is important to study if neurons isolated from different regions have similar, or opposite, reactions when in the presence HUCPVCs secretome (in the form of conditioned media-CM). In this work we: 1) studied how cortical and cerebellar neuronal primary cultures behaved when incubated with HUCPVCs CM and 2) characterized the differences between CM collected at two different conditioning time points. Primary cultures of cerebellar and cortical neurons were incubated with HUCPVCs CM (obtained 24 and 96 hours after three days of culturing). HUCPVCs CM had a higher impact on the metabolic viability and proliferation of cortical cultures, than the cerebellar ones. Regarding neuronal cell densities it was observed that with 24h CM condition there were higher number MAP-2 positive cells, a marker for fully differentiated neurons; this was, once again, more evident in cortical cultures. In an attempt to characterize the differences between the two conditioning time points a proteomics approach was followed, based on 2D Gel analysis followed by the identification of selected spots by tandem mass spectrometry.Results revealed important differences in proteins that have been previously related with phenomena such as neuronal cell viability, proliferation and differentiation, namely 14-3-3, UCHL1, hsp70 and peroxiredoxin-6. In summary, we demonstrated differences on how neurons isolated from different brain regions react to HUCPVCs secretome and we have identified different proteins (14-3-3 and hsp70) in HUCPVCs CM that may explain the above referred results M

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Section: Introductionmentioning

confidence: 99%

Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations

et al. 2013

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“…MSCs generally have a relatively short half-life which limits their ability to heal damaged tissue [84]. A major goal for the field should be to develop [10]. Hypoxic preconditioning has garnered some beneficial effects in this regard, but more investigation is needed [8].…”

Section: Discussionmentioning

confidence: 99%

“…MSCs can be isolated from bone marrow, umbilical cord and adipose tissue [9]. MSCs express the mesenchymal markers CD105, CD90, and CD73 but express few HLA class I and no HLA class II molecules, allowing them to evade allogeneic immune response, making them well suited for allogenic use [10].…”

Section: Phenotype Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell-based therapy for ischemic stroke

et al. 2016

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Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

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“…Mesenchymal stem cells have been pursued for this purpose because of both their wide differentiation potential and long life span, as well as their ability to home to bone marrow. (20) Even cell-based therapies, however, are not always robust enough with native cells; cells need to be genetically modified to express factors for improved potency. The patient's own cells would be the most favorable option for therapy to circumvent any potential immune response.…”

Section: J Jbmrmentioning

confidence: 99%

Realizing the potential of gene-based molecular therapies in bone repair

Rose

Uludağ

2013

Journal of Bone and Mineral Research

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A better understanding of osteogenesis at genetic and biochemical levels is yielding new molecular entities that can modulate bone regeneration and potentially act as novel therapies in a clinical setting. These new entities are motivating alternative approaches for bone repair by utilizing DNA-derived expression systems, as well as RNA-based regulatory molecules controlling the fate of cells involved in osteogenesis. These sophisticated mediators of osteogenesis, however, pose unique delivery challenges that are not obvious in deployment of conventional therapeutic agents. Viral and nonviral delivery systems are actively pursued in preclinical animal models to realize the potential of the gene-based medicines. This article will summarize promising bone-inducing molecular agents on the horizon as well as provide a critical review of delivery systems employed for their administration. Special attention was paid to synthetic (nonviral) delivery systems because they are more likely to be adopted for clinical testing because of safety considerations. We present a comparative analysis of dose-response relationships, as well as pharmacokinetic and pharmacodynamic features of various approaches, with the purpose of clearly defining the current frontier in the field. We conclude with the authors' perspective on the future of genebased therapy of bone defects, articulating promising research avenues to advance the field of clinical bone repair. © 2013 American Society for Bone and Mineral Research. KEY WORDS: OSTEOGENESIS; BIOENGINEERING; MOLECULAR PATHWAYS; GENE-BASED THERAPYClinical Need for New Bone-Regeneration Strategies N early 2.2 million bone grafts are performed worldwide annually (1) and up to 20% of fractures are hampered by impaired healing. (2) The economic impact of nonunions is enormous, with the cost of spinal fusions alone reaching $20 billion annually. (3) The gold standard for repair of large segmental defects remains autologous grafts, where bone harvested from a non-weight-bearing site, usually the iliac crest, is used to repair defects. Bone grafts, however, are limited in several aspects, including potency of the grafts and the physiological detriment resulting from harvest surgery. Allografts are alternatively employed, where donor tissue is used to repair the defect, but the risk of disease transmission is always a concern. Allografts are extensively processed to reduce this risk, but osteopotency of the graft could be decreased in this way. (4) Demineralized bone matrix derived from decalcified bone can similarly act as a substitute; its potency, however, is variable and depends on the processing conditions. Synthetic scaffolds have been used to provide a hospitable environment for new bone formation. Scaffolds have been constructed from the organic (collagen) and inorganic (hydroxyapatite [HA]) components of bone, but such scaffolds are incapable of inducing osteogenesis on their own and they are more suitable for smaller defects.Osteogenic proteins are frequently employed to render ost...

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Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors

Cited by 157 publications

References 79 publications

Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations

Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations

Mesenchymal stem cell-based therapy for ischemic stroke

Realizing the potential of gene-based molecular therapies in bone repair

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