There was a recent article that I found difficult to read without looking up many terms. It seemed worthwhile to use it as a learning exercise. Here’s the original article (an abstract):
2017-06-30: “Human Umbilical Cord Mesenchymal Stem Cells Protect Against SCA3 by Modulating the Level of 70 kD Heat Shock Protein”
Here it is broken down:
Spinocerebellar ataxia 3 (SCA3), which is a progressive neurodegenerative disease, is currently incurable. Emerging studies have reported that human umbilical cord mesenchymal stem cells (HUC-MSCs) transplantation could be a promising therapeutic strategy for cerebellar ataxias.
The significance of the umbilical cord is the presence of cord blood, which contains primitive stem cells. The donor need not be the recipient (see: allogeneic), so no, your mother need not have banked your umbilical cord (compare: autologous). The main alternative sources for stem cells are peripheral blood (deoxygenated, venous blood) and bone marrow, though it’s unclear to me whether this paper is saying there’s something unique about HUC-MSCs that would be absent from other types of stem cells.
Note that neural stem cells (NSCs) are generated in the embryonic stage, and if neurons in the brain die, then they cannot be replaced (except for a few rare exceptions). Stem cells transplanted into the brain will not cause them to differentiate into replacement neurons.
Mesenchymal: relating to embryonic tissue used in the umbilical cord, the vitreous (gel-like substance resembling glass) of the eyeball, etc.
Mesenchymal stem cells: a class of multipotent adult stem cells that generates connective tissues (including cartilage, tendons, and bone).
Transplant: move or transfer something to another place or situation, typically with some effort or upheaval.
Why the word transplantation here? Unless we are talking about maternal twins or using your own stem cells, stem cells of the donor have DNA that is different from the recipient, so there is kind of an implied upheaval.
However, few studies have evaluated the effects of HUC-MSCs on SCA3 transgenic mouse.
We know transgenic mice from the last time I created a page like this. But human stem cells transplanted into mice?? That is odd.
Thus, we investigated the effects of HUC-MSCs on SCA3 mice and the underlying mechanisms in this study. SCA3 transgenic mice received systematic administration of 2 × 106 HUC-MSCs once per week for 12 continuous weeks.
Not sure of the units (106). I’ll assume the 2x means twice in one day.
I wonder what administration method was used (ICBI? CVC (doubtful in mice)?).
Motor coordination was measured blindly by open field tests and footprint tests.
I’ll assume the meaning is what is intuitively obvious.
Immunohistochemistry [staining] and Nissl staining were applied to detect neuropathological alternations.
Staining: Stains and dyes are used to highlight structures in biological tissues for viewing, often with the aid of microscopes.
Immunohistochemistry (IHC): the roots are immuno, in reference to antibodies used in the procedure, and histo, meaning tissue. IHC staining is used in the diagnosis of abnormal cells.
Nissl staining: a nucleic acid (related to DNA/RNA) staining method used on nervous tissue sections. Named after Franz Nissl.
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole-body autopsies.
Alternation: the repeated occurrence of two things in turn. I wonder if this is a misspelling of alteration.
Neurotrophic factors in the cerebellum were assessed by ELISA.
Trophic: relating to feeding and nutrition.
Neurotrophic: relating to the growth of nervous tissue.
Neurotrophic factors (NTFs): a family of biomolecules that support the growth and survival of neurons.
ELISA: Enzyme-linked immunosorbent assay (ELISA) is a test that uses antibodies and color change to identify a substance.
We used western blotting to detect the alternations of heat shock protein 70 (HSP70), IGF-1, mutant ataxin-3, and apoptosis-associated proteins.
I wonder, again, if alternation is misspelled (or misused).
Blot: a method of transferring proteins, DNA, or RNA onto a carrier so they can be visualized by colorant staining.
Western blot: The western blot (sometimes called the protein immunoblot) is a technique for detecting specific proteins in a tissue sample. (The name is a pun, keying off a related method named after Edwin Southern.)
Heat shock: the effect of subjecting a cell to a higher temperature than that of the ideal body temperature. Heat shock can cause proteins (created by the cells) to misfold, aggregate, and/or entangle.
Heat shock protein (HSP): a family of (protective?) proteins that are produced by cells in response to exposure to stressful conditions.
Heat shock protein 70 (HSP70): a family of ubiquitously expressed heat shock proteins. They are an important part of the cell’s machinery for protein folding and help to protect cells from stress. The 70 comes from weighing 70 kilodaltons.
Insulin-like growth factor 1 (IGF-1): a hormone similar in molecular structure to insulin. It plays an important role in childhood growth and continues to have anabolic effects in adults (relating to the synthesis of complex molecules for the storage of energy).
Mutant ataxin-3: the underlying protein problem that SCA3 causes!
Apoptosis: programmed cell death (i.e., planned, expected, necessary; thereby efficient and cleaned up) aka “cellular suicide.” As opposed to necrosis, which is traumatic cell death.
Apoptosis-associated proteins: proteins found to be present during the apoptosis process.
Tunel staining was also used to detect apoptosis of affected cells.
TUNEL: stands for TdT (Terminal Deoxynucleotidyl Transferase)-Mediated dUTP (2′-Deoxyuridine 5′-Triphosphate) Nick-End Labeling. It is a method for detecting DNA fragmentation during apoptosis.
This wins the prize for ugliest acronym expansion ever.
The distribution and differentiation of HUC-MSCs were determined by immunofluorescence.
Differentiation: stem cells changing into a specific cell type.
Immunofluorescence: a technique that uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell and therefore allows visualization of the distribution of the target molecule through the sample.
Our results exhibited that HUC-MSCs transplantation significantly alleviated motor impairments, corresponding to a reduction of cerebellar atrophy, preservation of neurons, decreased expression of mutant ataxin-3, and increased expression of HSP70.
Understandable now.
Implanted HUC-MSCs were mainly distributed in the cerebellum and pons with no obvious differentiation, and the expressions of IGF-1, VEGF, and NGF in the cerebellum were significantly elevated.
Stem cells, administered in an unspecified way, ended up both in the cerebellum and pons. In other words, targeting wasn’t specific to the cerebellum either by choice or by outcome.
Vascular endothelial growth factor (VEGF): a signal protein produced by cells that stimulates the formation of blood vessels. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions.
Nerve growth factor (NGF): protein-like molecules primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons.
Elevated? Apparently, boosting these levels is good.
Furthermore, with the use of HSP70 analogy quercetin injection, it demonstrated that HSP70 is involved in mutant ataxin-3 reduction.
Biological analogy: normally, this would refer to a commonality between transgenic mice and humans.
Quercetin: an antioxidant, readily available in supplement form. I’ve taken it as a natural anti-inflammatory.
I wonder about the word analogy here. It could be that something else was meant. The web indicates that quercitin inhibits HSP expression.
These results showed that HUC-MSCs implantation is a potential treatment for SCA3, likely through upregulating the IGF-1/HSP70 pathway and subsequently inhibiting mutant ataxin-3 toxicity.
Upregulation: essentially an increase.
Back to the title:
Human Umbilical Cord Mesenchymal Stem Cells Protect Against SCA3 by Modulating the Level of 70 kD Heat Shock Protein
Translation: Stem cells protect against SCA3 by triggering an increase in protein protectants.
In my opinion, this whole song and dance is still disease amelioration at best.
Other
On the topic of stem cells (but not this article), it’s good to know what potency refers to: the potential of stem cells to differentiate into different cell types. The different potencies: totipotent (aka omnipotent) / pluripotent / multipotent / oligopotent / unipotent.
Addendum—2018 trial
I’m not a proponent of stem cells and SCA; I’m just trying to keep up with what’s going on. There is a phase 2 trial beginning 2018 January, planned for two years, sponsored by a Chinese company called SCLnow Biotechnologies, who has a low-quality website; offline on 2022-08-12.
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