Mobilization, Isolation and Characterization of Stem Cells from Peripheral Blood: a Systematic Review

Yosupov, Natali; Haimov, Haim; Juodžbalys, Gintaras

doi:10.5037/jomr.2017.8101

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…Importantly, our study demonstrates that the REST pathway is active in MPCs. MPCs are abundant at the site of traumatic injury and may therefore be a clinically useful source of autologous cells, circumventing the issues associated with the scarcity of Schwann cells or mobilization of MSCs from the bone marrow 26,27 . We have previously shown that MPCs possess neurotrophic properties equivalent to those of MSCs, and express BDNF at significantly higher levels 23 .…”

Section: Discussionmentioning

confidence: 99%

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

Gervasi

Dimtchev

Clark

et al. 2021

Sci Rep

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Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. As targeting of transcription factors is challenging, we tested whether modulation of REST activity could be achieved through knockdown of carboxy-terminal domain small phosphatase 1 (CTDSP1), the enzyme that stabilizes REST by preventing its targeting to the proteasome. To test whether knockdown of CTDSP1 promotes neurotrophic factor expression in both support cells located at the site of injury and in peripheral neurons, we transfected mesenchymal progenitor cells (MPCs), a type of support cells that are present at high concentrations at the site of injury, and dorsal root ganglion (DRG) neurons with REST or CTDSP1 specific siRNA. We quantified neurotrophic factor expression by RT-qPCR and Western blot, and brain-derived neurotrophic factor (BDNF) release in the cell culture medium by ELISA, and we measured neurite outgrowth of DRG neurons in culture. Our results show that CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs, and promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may, therefore, represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.

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Section: Discussionmentioning

confidence: 99%

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

Gervasi

Dimtchev

Clark

et al. 2021

Sci Rep

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show abstract

“…Importantly, our study demonstrates that the REST pathway is active in MPCs. MPCs are abundant at the site of traumatic injury and may therefore be a clinically useful source of autologous cells, circumventing the issues associated with the scarcity of Schwann cells or mobilization of MSCs from the bone marrow [24,25]. We have previously shown that MPCs possess neurotrophic properties equivalent to those of MSCs, and express BDNF at signi cantly higher levels [18].…”

Section: Discussionmentioning

confidence: 99%

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration

Gervasi¹,

Dimitchev²,

Clark³

et al. 2020

Preprint

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Background: Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. REST is stabilized by the Carboxy-terminal domain small phosphatase 1 (CTDSP1), which prevents REST targeting to the proteasome. Here, we explore whether knockdown of CTDSP1 promotes neurotrophic factor expression in mesenchymal progenitor cells (MPCs), a type of support cells that can be harvested from the site of injury during surgical debridement, and in dorsal root ganglion (DRG) neurons. In addition, we explore whether CTDSP1 knockdown supports DRG neurite regeneration. Methods: Cultured human MPCs or rat DRG neurons were transfected with REST or CTDSP1 specific siRNA. Neurotrophic factor expression was analyzed by RT-qPCR and Western Blot. Brain-derived Neurotrophic Factor (BDNF) in cell culture medium was quantified by ELISA. Axon regeneration was quantified measuring the length of the longest neurite of a neuron. Results: Knockdown of REST or CTDSP1 in MPCs results in increased expression of BDNF and nerve growth factor (NGF). In addition, knockdown of CTDSP1 leads to increased release of BDNF in cell culture medium from MPCs and to reduced levels of REST protein. Finally, knockdown of CTDSP1 in DRG neurons results in increased levels of BDNF and increased DRG neurite growth rate.Conclusions: CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs. In addition, it promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.

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“…Antimicrobial and antiviral prophylaxis was routinely administered. Blood samples were tested for EBV and CMV using polymerase chain reaction (PCR) testing [13,14].…”

Section: Ratg and Gvhd Prophylaxismentioning

confidence: 99%

Reduced risk of chronic GVHD by low-dose rATG in adult matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

Dou

Hou

et al. 2019

Ann Hematol

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The optimal rabbit anti-thymocyte globulin (rATG) graft-versus-host disease (GVHD) prophylaxis regimen in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. In this prospective study, we used lowdose rATG for GVHD prophylaxis in patients or donors aged ≥ 40 years with hematological malignancies receiving MSD-PBSCT. rATG was administered to 40 patients at an intravenous dose of 5 mg/kg divided over day 5 and day 4 before graft infusion. No graft failure occurred. Median times to leukocyte engraftment and platelet engraftment were 11.0 days and 13.9 days. The cumulative incidence of grades 2-4 and grades 3-4 acute GVHD at day +100 was 30.0% and 2.6%. The 2-year cumulative incidence of extensive chronic GVHD and severe chronic GVHD was 11.4% and 14.7%. 93.5% (29/31) of patients had discontinued immunosuppressive medication within 3 years after transplantation. The 2-year cumulative incidence of transplant-related mortality (TRM) and relapse was 14.0% and 22.6%. The cumulative incidence of cytomegalovirus reactivation, Epstein-Barr virus reactivation, and fungal infection was 22.3%, 12.9%, and 12.5%. Kaplan-Meier estimates for overall survival, disease-free survival, and GVHD-free and relapse-free survival 3 years after transplantation were 68.9%, 68.9%, and 54.0%. rATG for GVHD prophylaxis is tolerable and efficacious at a 5 mg/kg total dose administered over 2 days (days −5 to −4) in patients receiving allogeneic MSD-PBSCT.

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Mobilization, Isolation and Characterization of Stem Cells from Peripheral Blood: a Systematic Review

Cited by 10 publications

References 37 publications

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration

Reduced risk of chronic GVHD by low-dose rATG in adult matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

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