Parkinson’s
 

     Parkinson’s Disease (PD) is a degenerative disorder of the central nervous system that affects close to one million Americans.  PD is a chronic and progressive disorder, which is thought to be caused by the destruction of dopamine (an important neurotransmitter) that generates cells in the midbrain.  The cause of PD is unknown and there is no cure.  Treatment is focused on medication and management of symptoms. Current research include investigations into new animal models of the disease, and of the potential use of gene therapy, stem cell transplants and neuro-protective agents. There is hope that mesenchymal stem cells will mitigate some of the degenerative effects.

     The Cell Surgical Network (CSN) has developed a specific deployment protocol that attempts to utilize the regenerative properties of stromal vascular fraction (SVF), which is rich in mesenchymal stem cells and growth factors. Special measures are taken to optimize transport of SVF across the blood-brain barrier to improve central nervous system uptake. This is completed in an outpatient setting at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately three hours.

     The Cell Surgical Network takes pride in the time provided to patients to follow the more currently updated protocols to help patients achieve their goals. By filling out our Confidential Candidate Application, we can then answer the questions or concerns you may have about our existing procedures for Parkinson’s Disease.

 
CANDIDATE APPLICATION
Human adipose-derived stem cells stimulate neuroregeneration.
2016 Aug;16(3):451-61. doi: 10.1007/s10238-015-0364-3. Epub 2015 Jun 6. Masgutov RF1,2, Masgutova GA1, Zhuravleva MN1, Salafutdinov II1,2, Mukhametshina RT1, Mukhamedshina YO1, Lima LM3, Reis HJ4, Kiyasov AP1, Palotás A5,6, Rizvanov AA7.
 
 
Abstract

Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves.

KEYWORDS:

Autonerve graft; Human adipose-derived stem cell (hADSC); Peripheral nerve injury; Regenerative medicine; Repair; Xenotransplantation

PMID:
26047869
 
 
Synergy Between Choroid Plexus Epithelial Cell-Conditioned Medium and Knockout Serum Replacement Converts Human Adipose-Derived Stem Cells to Dopamine-Secreting Neurons.
2017 Aug;20(4):309-319. doi: 10.1089/rej.2016.1887. Epub 2017 Apr 27. Boroujeni ME, Gardaneh M, Shahriari MH, Aliaghaei A, Hasani S.
 
Abstract

Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as nonmesodermal lineages, including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of choroid plexus epithelial cell-conditioned medium (CPEC-CM) alone or cocktailed with knockout serum (KS) to induce dopaminergic (DAergic) differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so that selected media easily differentiated them into osteoblasts, chondrocytes, and adipocytes. To begin inducing hADSC neuronal differentiation, we isolated CPECs from rat brain and expanded them in culture to obtain CPEC-CM. We then treated hADSCs with optimized quantities of collected CPEC-CM, KS, or both. The ADSCs treated with either CPEC-CM or CPEC-CM and KS displayed morphological changes typical of neuron-like phenotypes. As revealed by reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), and immunostaining analyses, hADSCs cotreated with CPEC-CM and KS expressed significantly higher levels of neuronal and DAergic markers in comparison with single-treated groups. Moreover, the hADSCs began expressing dopamine-biosynthesizing enzymes mainly after cotreatment with CPEC-CM and KS. Consequently, only cotreated hADSCs were capable of synthesizing and releasing dopamine detectable by high-performance liquid chromatography (HPLC). Finally, hADSCs growing in an ordinary medium were found positive for astrocytic marker glial fibrillary acidic protein (GFAP), but stopped GFAP expression on either single or cotreatments. These combined results suggest that CPEC-CM and KS can synergize to remarkably augment DAergic induction of hADSCs, an effect that has implications for cell replacement therapy for PD and related disorders.

KEYWORDS: Parkinson's disease; adipose-derived stem cells; choroid plexus; dopaminergic
PMID: 28437187
 
 
Stem cell-based approach for the treatment of Parkinson's disease.
 
 
Abstract

Parkinson's disease (PD) is the second most common neurodegenerative brain disorder which is around 1.5 times more common in men than in women. Currently, drug medications, surgery, and lifestyle changes are common approaches to PD, while all of them focused on reducing the symptoms. Therefore, regenerative medicine based on stem cell (SC) therapies has raised a promising hope. Various types of SCs have been used in basic and experimental studies relevant to PD, including embryonic pluripotential stem cells, mesenchymal (MSCs) and induced pluripotent SCs (iPSCs). MSCs have several advantages over other counterparts. They are easily accessible which can be obtained from various tissues such as bone marrow, adipose tissue, peripheral blood, etc. with avoiding ethical problems. Therefore, MSCs is attractive clinically because there are no related ethical and immunological concerns . Further studies are needed to answer some crucial questions about the different issues in SC therapy. Accordingly, SC-based therapy for PD also needed more complementary evaluation in both basic and clinical study areas.

KEYWORDS: Cellular therapy; Neurodegenerative diseases; Parkinson’s disease; Stem cell
PMID: 26000262
 
 
Adipose-derived human mesenchymal stem cells induce long-term neurogenic and anti-inflammatory effects and improve cognitive but not motor performance in a rat model of Parkinson's disease.
 
2015 May;10(4):431-46. doi: 10.2217/rme.15.17. Schwerk A, Altschüler J, Roch M, Gossen M, Winter C, Berg J, Kurtz A, Akyüz L, Steiner B.
 
Abstract
 
BACKGROUND: Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease.
METHODS: MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6 months.
RESULTS:MSC localized around the substantia nigra and the arachnoid mater, expressing pericyte and endothelial markers. MSC protected dopamine levels and upregulated peripheral anti-inflammatory cytokines. Furthermore, adipose-derived MSC increased neurogenesis in hippocampal and subventricular regions, and boosted memory functioning.
CONCLUSION:Considering that hyposmia and loss of memory function are two major nonmotor symptoms in Parkinson's disease, transplants with modulatory effects on the hippocampus and subventricular zone could provide a disease-modifying therapy.
 
 
Adipose-derived human mesenchymal stem cells induce long-term neurogenic and anti-inflammatory effects and improve cognitive but not motor performance in a rat model of Parkinson's disease.
 
2015 May;10(4):431-46. doi: 10.2217/rme.15.17. Schwerk A, Altschüler J, Roch M, Gossen M, Winter C, Berg J, Kurtz A, Akyüz L, Steiner B.
 
 
Abstract
 
BACKGROUND: Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease.
METHODS: MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6 months.
RESULTS:MSC localized around the substantia nigra and the arachnoid mater, expressing pericyte and endothelial markers. MSC protected dopamine levels and upregulated peripheral anti-inflammatory cytokines. Furthermore, adipose-derived MSC increased neurogenesis in hippocampal and subventricular regions, and boosted memory functioning.
CONCLUSION:Considering that hyposmia and loss of memory function are two major nonmotor symptoms in Parkinson's disease, transplants with modulatory effects on the hippocampus and subventricular zone could provide a disease-modifying therapy.
 
 
Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson's disease related toxin 6-hydroxydopamine.
2017 Dec;121:113-120. doi: 10.1016/j.ejpb.2017.09.014. Epub 2017 Sep 28. Chierchia A1, Chirico N2, Boeri L2, Raimondi I1, Riva GA2, Raimondi MT2, Tunesi M3, Giordano C3, Forloni G1, Albani D4.
 
Abstract

Neurodegenerative diseases, as Parkinson's disease (PD), involve irreversible neural cell damage and impairment. In PD, there is a selective degeneration of the dopaminergic neurons leading to motor symptoms. A common finding in PD neurodegeneration is the increase of reactive oxygen species (ROS), leading to oxidative stress. To date there are only interventions to relieve PD symptoms, however progress has been made in the development of therapies that target the immune system or use its components as therapeutic agents; among these, mesenchymal stem cells (MSCs), which are able to express neuroprotective factors as cytokines, chemokines and angiogenic molecules, collectively named secretome, that accumulate in MSC culture medium. However, lasting cell-free administration of secretome in vitro or in vivo is challenging. We used the conditioned media from rat adipose tissue-derived MSCs (RAA-MSCs) to check for neuroprotective activity towards pro-oxidizing agents such as hydrogen peroxide (H2O2) or the dopaminergic selective toxin 6-hydroxydopamine (6-OHDA) that is commonly used to model PD neurodegeneration. When neuroblastoma SH-SY5Y cells were pre-conditioned with 100% RAA-MSC media, then treated with H2O2 and 6-OHDA, mortality and ROS generation were reduced. We implemented the controlled release of RAA-MSC secretome from injectable biodegradable hydrogels that offer a possible in situ implant with mini-invasive techniques. The hydrogels were composed of type I bovine collagen (COLL) and low-molecular-weight hyaluronic acid (LMWHA) or COLL and polyethylene glycol (PEG). Hydrogels were suitable for RAA-MSC embedding up to 48h and secretome from these RAA-MSCs was active and counteracted 6-OHDA toxicity, with upregulation of the antioxidant enzyme sirtuin 3 (SIRT3). These results support a biomaterials-based approach for controlled delivery of MSC-produced neuroprotective factors in a PD-relevant experimental context.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS: 3D cell culture; Adipose mesenchymal stem cells; Hydrogel; Parkinson’s disease; Secretome
PMID: 28965958
 
 
Therapeutic potentials of human adipose-derived stem cells on the mouse model of Parkinson's disease.
2015 Oct;36(10):2885-92. doi: 10.1016/j.neurobiolaging.2015.06.022. Epub 2015 Jun 24. Choi HS, Kim HJ, Oh JH, Park HG, Ra JC, Chang KA, Suh YH.
 
Abstract

The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS: 6-OHDA; Human adipose-derived stem cells; Mitochondria; Parkinson's disease
PMID: 26242706
 
[bot_catcher]