Messages

1

The Waiting Room / Any basketball players here?

« on: March 03, 2022, 10:23:17 PM »

Oh boy. Went shooting the other day. Very mild stuff, taking jumpers only and not playing in any half or full court games.

Ankle felt like it had been through the meat grinder afterwards. Yikes

2

Ankle / Re: Bulk allograft?

« on: May 06, 2021, 09:28:46 AM »

My OATS has failed

Dang pds I'm so sorry. That sucks..

Afraid I can't help with having any exp. with allografts.
My thoughts are with you.

I wonder if you could email some more doctors and ask them? Maybe some would respond.

What other options are available to you?

and how's the pain right now?

3

The Waiting Room / Re: An Emotional Test

« on: March 17, 2021, 11:50:51 PM »

Thanks for sharing your insights on the emotions involved. I knew I wasn't the only one.

What makes this somewhat unique among injuries is the lack of knowledge and clear path involved, which makes it harder to move through the 5 stages of grief. We're never quite sure where we should be on the 5 stages because while some of us have made it to 'Acceptance' (5th and final stage), there are still glimmers of hope from the next surgery, whether it be another MF, OATs, denovo, or stem cell fantasies.

So we're forever in this kind of limbo stage in between Depression and Acceptance (4th and 5th stages) or Acceptance and something else like hope (5th and xth stages), just kind of waiting around, sometimes bouncing back to the 3rd stage (bargaining) and then beginning the cycle again.


Me, i've been in a kind of apathetic acceptance stage for 15 years, during which I haven't really done much research, but there is a stage beyond that, which is HOPE lol. Every so often i pop back in and see if there's any surgery options that could fully restore my ankle. Right now OATS isn't worth the risk to me because my ankle is at around 60% and I can still walk on it. I still have hope of something groundbreaking coming out. Maybe i'll need to wait another 15 years.

4

Ankle - Future treatments / Adult Humans can regenerate cartilage (2019)

« on: March 17, 2021, 10:46:00 PM »

https://www.the-scientist.com/news-opinion/adult-humans-can-regenerate-cartilage--study-66558

Humans, unlike some lucky members of the animal kingdom, have a very limited ability to regrow damaged or missing body parts. But a study published yesterday (October 9) in Science Advances finds that we can generate new proteins in joint cartilage, and this ability is more pronounced in joints farther from the center of the body, such as the ankles, than in those nearer in, such as the hips. The mechanism for this ability resembles that used by animals such as salamanders and axolotls to regrow lost limbs.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” says coauthor Virginia Kraus, who researches osteoarthritis at Duke University School of Medicine, in a university press release.

Kraus and her colleagues analyzed proteins from cartilage tissue from human hips, knees, and ankles for changes to amino acids that occur with time. “We suddenly started noticing that the ankle proteins tended by and large to be much younger than the same proteins in the knee and the same proteins in the hip,” Kraus tells The Guardian.

The researchers found that the prevalence of younger proteins was tied to the abundance of a microRNA that blocks the action of a messenger RNA that inhibits the production of new collagen proteins. Similar microRNAs are active in animals that can regrow limbs, the authors note—and, as in humans, the animals’ regeneration ability is greater in distal parts of the body than in more central ones.

Writing to Gizmodo, Kraus says she is “very hopeful” that the findings could lead to therapies. Potentially, she suggests, microRNAs could be “injected directly into a joint to boost repair to prevent osteoarthritis after a joint injury or even slow or reverse osteoarthritis once it has developed.”

“It is amazing to find that although we humans have separated from the axolotl 400 million years ago in evolution, there are many pathways that are commonly shared between human and axolotl,” writes Prayag Murawala, a postdoc at the Research Institute of Molecular Pathology in Vienna, Austria, in an email to Gizmodo. Murawala, who was not involved in the study, adds that “although we still have a long way to go to explain why humans cannot regenerate, this study provides compelling evidence that there are many similarities in human and salamander limbs.”

5

Ankle - Future treatments / Re: Researchers find method to regrow cartilage in the joints (STANFORD)

« on: March 17, 2021, 10:40:52 PM »

the previous study they built on: https://med.stanford.edu/news/all-news/2018/09/study-identifies-stem-cell-that-gives-rise-to-new-bone-cartilage.html

Study identifies stem cell that gives rise to new bone, cartilage in humans
Identification of the human skeletal stem cell by Stanford scientists could pave the way for regenerative treatments for bone fractures, arthritis and joint injuries.

A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

The cell, which can be isolated from human bone or generated from specialized cells in fat, gives rise to progenitor cells that can make new bone, the spongy stroma of the bone’s interior and the cartilage that helps our knees and other joints function smoothly and painlessly.

The discovery allowed the researchers to create a kind of family tree of stem cells important to the development and maintenance of the human skeleton. It could also pave the way for treatments that regenerate bone and cartilage in people.

“Every day, children and adults need normal bone, cartilage and stromal tissue,” said Michael Longaker, MD, professor of plastic and reconstructive surgery. “There are 75 million Americans with arthritis, for example. Imagine if we could turn readily available fat cells from liposuction into stem cells that could be injected into their joints to make new cartilage, or if we could stimulate the formation of new bone to repair fractures in older people.”

A paper describing the finding was published online Sept. 20 in Cell.

Longaker, the Deane P. and Louise Mitchell Professor in the School of Medicine and the co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, is the senior author. The lead authors are Charles K.F. Chan, PhD, assistant professor of surgery; medical student Gunsagar Gulati, MD; Rahul Sinha, PhD, instructor of stem cell biology and regenerative medicine; and research assistant Justin Vincent Tompkins.

‘True, multipotential, self-renewing’
The skeletal stem cells are distinct from another cell type called the mesenchymal stem cell, which can generate skeletal tissues, fat and muscle. Mesenchymal stem cells, which can be isolated from blood, bone marrow or fat, are considered by some clinicians to function as all-purpose stem cells. They have been tested, with limited success, in clinical trials and as unproven experimental treatments for their ability to regenerate a variety of tissues. Recently, three elderly patients in Florida were blinded or lost most of their sight after mesenchymal stem cells from fat were injected into their eyes as an experimental treatment for macular degeneration.

“Mesenchymal stem cells are loosely characterized and likely to include many populations of cells, each of which may respond differently and unpredictably to differentiation signals,” Chan said. “In contrast, the skeletal stem cell we’ve identified possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells. They are restricted in terms of their fate potential to just skeletal tissues, which is likely to make them much more clinically useful.”

Skeletal regeneration is an important capability for any bony animal evolving in a rough-and-tumble world where only the most fit, or the fastest-healing, are likely to survive very long into adulthood. Some vertebrates, such as newts, are able to regenerate entire limbs if necessary, but the healing ability of other animals, such as mice and humans, is more modest. Although humans can usually heal a bone fracture fairly well, they begin to lose some of that ability with age. And they are completely unable to regenerate the cartilage that wears away with age or repetitive use. Researchers have wondered whether the skeletal stem cell could be used clinically to help replace damaged or missing bone or cartilage, but it’s been very difficult to identify.

Adult stem cells lineage-restricted
Unlike embryonic stem cells, which are present only in the earliest stages of development, adult stem cells are thought to be found in all major tissue types, where they bide their time until needed to repair damage or trauma. Each adult stem cell is lineage-restricted — that is, it makes progenitor cells that give rise only to the types of cells that naturally occur in that tissue. For our skeleton, that means cells that make bone, cartilage and stroma.

Michael Longaker
Michael Longaker

Chan, Longaker and their colleagues had hoped to use what they learned from identifying the mouse skeletal stem cell to quickly isolate its human counterpart. But the quest turned out to be more difficult than they had anticipated. Most cell isolation efforts focus on using a technology called fluorescence activated cell sorting to separate cells based on the expression of proteins on their surface. Often, similar cell types from different species share some key cell surface markers.

But the human skeletal stem cell turned out to share few markers with its mouse counterpart. Instead, the researchers had to compare the gene expression profiles of the mouse skeletal stem cell with those of several human cell types found at the growing ends of developing human bone. Doing so, they were able to identify a cell population that made many of the same proteins as the mouse skeletal stem cell. They then worked backward to identify markers on the surface of the human cells that could be used to isolate and study them as a pure population.

“This was quite a bioinformatics challenge, and it required a big team of interdisciplinary researchers, but eventually Chuck and his colleagues were able to identify a series of markers that we felt had great potential,” Longaker said. “Then they had to prove two things: Can these cells self-renew, or make more of themselves indefinitely, and can they make the three main lineages that comprise the human skeleton?”

The researchers showed that the human skeletal stem cell they identified is both self-renewing and capable of making bone, cartilage and stroma progenitors. It is found at the end of developing bone, as well as in increased numbers near the site of healing fractures. Not only can it be isolated from fracture sites, it can also be generated by reprogramming human fat cells or induced pluripotent stem cells to assume a skeletal fate.

‘The perfect niche’
Intriguingly, the skeletal stem cell also provided a nurturing environment for the growth of human hematopoietic stem cells — or the cells in our bone marrow that give rise to our blood and immune system — without the need for additional growth factors found in serum.

“Blood-forming stem cells love the interior of spongy bone,” Chan said. “It’s the perfect niche for them. We found that the stromal population that arises from the skeletal stem cell can keep hematopoietic stem cells alive for two weeks without serum.”

By studying the differentiation potential of the human skeletal stem cell, the researchers were able to construct a family tree of stem cells to serve as a foundation for further studies into potential clinical applications. Understanding the similarities and differences between the mouse and human skeletal stem cell may also unravel mysteries about skeletal formation and intrinsic properties that differentiate mouse and human skeletons.

The skeletal stem cell we’ve identified possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells.
“Now we can begin to understand why human bone is denser than that of mice, or why human bones grow to be so much larger,” Longaker said.

In particular, the researchers found that the human skeletal stem cell expresses genes active in the Wnt signaling pathway known to modulate bone formation, whereas the mouse skeletal stem cell does not. 

The ultimate goal of the researchers, however, is to find a way to use the human skeletal stem cell in the clinic. Longaker envisions a future in which arthroscopy — a minimally invasive procedure in which a tiny camera or surgical instruments, or both, are inserted into a joint to visualize and treat damaged cartilage — could include the injection of a skeletal stem cell specifically restricted to generate new cartilage, for example.

“I would hope that, within the next decade or so, this cell source will be a game-changer in the field of arthroscopic and regenerative medicine,” Longaker said. “The United States has a rapidly aging population that undergoes almost 2 million joint replacements each year. If we can use this stem cell for relatively noninvasive therapies, it could be a dream come true.”

6

Ankle - Future treatments / Researchers find method to regrow cartilage in the joints (STANFORD) (2020, Aug)

« on: March 17, 2021, 10:39:30 PM »

https://med.stanford.edu/news/all-news/2020/08/Researchers-find-method-to-regrow-cartilage-in-the-joints.html

In laboratory studies, Stanford School of Medicine researchers have found a way to regenerate the cartilage that eases movement between bones.

Researchers at the Stanford University School of Medicine have discovered a way to regenerate, in mice and human tissue, the cushion of cartilage found in joints.

Loss of this slippery and shock-absorbing tissue layer, called articular cartilage, is responsible for many cases of joint pain and arthritis, which afflicts more than 55 million Americans. Nearly 1 in 4 adult Americans suffer from arthritis, and far more are burdened by joint pain and inflammation generally.

The Stanford researchers figured out how to regrow articular cartilage by first causing slight injury to the joint tissue, then using chemical signals to steer the growth of skeletal stem cells as the injuries heal. The work was published Aug. 17 in the journal Nature Medicine.

“Cartilage has practically zero regenerative potential in adulthood, so once it’s injured or gone, what we can do for patients has been very limited,” said assistant professor of surgery Charles K.F. Chan, PhD. “It’s extremely gratifying to find a way to help the body regrow this important tissue.”

The work builds on previous research at Stanford that resulted in isolation of the skeletal stem cell, a self-renewing cell that is also responsible for the production of bone, cartilage and a special type of cell that helps blood cells develop in bone marrow. The new research, like previous discoveries of mouse and human skeletal stem cells, were mostly carried out in the laboratories of Chan and professor of surgery Michael Longaker, MD.

Articular cartilage is a complex and specialized tissue that provides a slick and bouncy cushion between bones at the joints. When this cartilage is damaged by trauma, disease or simply thins with age, bones can rub directly against each other, causing pain and inflammation, which can eventually result in arthritis.

Chan
Charles K.F. Chan

Damaged cartilage can be treated through a technique called microfracture, in which tiny holes are drilled in the surface of a joint. The microfracture technique prompts the body to create new tissue in the joint, but the new tissue is not much like cartilage.

 “Microfracture results in what is called fibrocartilage, which is really more like scar tissue than natural cartilage,” said Chan. “It covers the bone and is better than nothing, but it doesn’t have the bounce and elasticity of natural cartilage, and it tends to degrade relatively quickly.” 

The most recent research arose, in part, through the work of surgeon Matthew Murphy, PhD, a visiting researcher at Stanford who is now at the University of Manchester. “I never felt anyone really understood how microfracture really worked,” Murphy said. “I realized the only way to understand the process was to look at what stem cells are doing after microfracture.” Murphy is the lead author on the paper. Chan and Longaker are co-senior authors.

For a long time, Chan said, people assumed that adult cartilage did not regenerate after injury because the tissue did not have many skeletal stem cells that could be activated. Working in a mouse model, the team documented that microfracture did activate skeletal stem cells. Left to their own devices, however, those activated skeletal stem cells regenerated fibrocartilage in the joint.

But what if the healing process after microfracture could be steered toward development of cartilage and away from fibrocartilage? The researchers knew that as bone develops, cells must first go through a cartilage stage before turning into bone. They had the idea that they might encourage the skeletal stem cells in the joint to start along a path toward becoming bone, but stop the process at the cartilage stage.

The researchers used a powerful molecule called bone morphogenetic protein 2 (BMP2) to initiate bone formation after microfracture, but then stopped the process midway with a molecule that blocked another signaling molecule important in bone formation, called vascular endothelial growth factor (VEGF).

“What we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get,” Chan said. “It also restored mobility to osteoarthritic mice and significantly reduced their pain.”

As a proof of principle that this might also work in humans, the researchers transferred human tissue into mice that were bred to not reject the tissue, and were able to show that human skeletal stem cells could be steered toward bone development but stopped at the cartilage stage.

The next stage of research is to conduct similar experiments in larger animals before starting human clinical trials. Murphy points out that because of the difficulty in working with very small mouse joints, there might be some improvements to the system they could make as they move into relatively larger joints.

The first human clinical trials might be for people who have arthritis in their fingers and toes. “We might start with small joints, and if that works we would move up to larger joints like knees,” Murphy says. “Right now, one of the most common surgeries for arthritis in the fingers is to have the bone at the base of the thumb taken out. In such cases we might try this to save the joint, and if it doesn’t work we just take out the bone as we would have anyway. There’s a big potential for improvement, and the downside is that we would be back to where we were before.”

Longaker points out that one advantage of their discovery is that the main components of a potential therapy are approved as safe and effective by the FDA. “BMP2 has already been approved for helping bone heal, and VEGF inhibitors are already used as anti-cancer therapies,” Longaker said. “This would help speed the approval of any therapy we develop.”

Joint replacement surgery has revolutionized how doctors treat arthritis and is very common: By age 80, 1 in 10 people will have a hip replacement and 1 in 20 will have a knee replaced. But such joint replacement is extremely invasive, has a limited lifespan and is performed only after arthritis hits and patients endure lasting pain. The researchers say they can envision a time when people are able to avoid getting arthritis in the first place by rejuvenating their cartilage in their joints before it is badly degraded.

 “One idea is to follow a ‘Jiffy Lube’ model of cartilage replenishment,” Longaker said. “You don’t wait for damage to accumulate — you go in periodically and use this technique to boost your articular cartilage before you have a problem.”

7

Ankle / Re: OATS Recovery Journal

« on: March 17, 2021, 10:23:52 PM »

hey PDS, that's great to hear that Kennedy found the root of the problem.

How's your ankle doing now? Hopefully so good that you don't have to post anymore! haha.

8

Ankle / Re: An OCD patient from Shanghai asks for advice

« on: May 12, 2020, 11:18:18 PM »

Hey Wade. sorry to hear about your injury.

Do you have an update on what option you went with? How's your ankle feeling now?

9

Ankle / Re: ***Poll - When improvement after microfracture***

« on: March 15, 2020, 11:25:55 PM »

12-15 months.

10

Ankle / Re: OCD Microdrilling post op questions

« on: October 18, 2019, 04:44:18 AM »

Hey Jodi. 10 weeks post-op sounds a bit early to be walking around.
I know that even after 12 weeks my ankle was super tender and i was keeping my activity limited to therapy and walking only short distances
I think MF took me a year to fully recover from to the point where I could walk around and not feel it

11

Ankle / Re: OATS insurance (denial appeals)

« on: April 11, 2019, 09:15:07 PM »

I thought it was matter of reviewing your health insurance policies and seeing if OATs is covered. Not sure what the surgeon has to do with it.
Your health insurance rep should be able to tell you...

12

Ankle / Re: OCD Surgery Advice Please :)

« on: April 11, 2019, 09:12:52 PM »

The sooner you let go of the sports and just accept what your ankle lets you do, the faster you will bounce back mentally.
It's the years  and years of waiting and holding out for the slim chance you can return to your old life (what they call Denial and Bargaining as part of the 5 stages of grief) that prevent you from moving on to the mindset that... man as long as you can walk on your two ankles without constant grinding pain.. it's better than not being able to.

I'm sorry this happened to you. Keep your head up and focus on what's in front of you: recovery from this MF surgery. Best of luck, let us know how you're doing or if you need more encouragement.

13

Ankle / Re: Cortizone injections question

« on: January 15, 2019, 09:26:40 PM »

It reduces inflammation, meaning might reduce some of the pain temporarily.
I had one cortizone shot and my ankle felt goood enough to go back to playing basketball . that only lasted two days though.
the OCD Pain came back not long after

14

OCD Surgeries / Re: Microfracture and OATS Updates

« on: November 27, 2018, 03:14:11 PM »

Thank you for the amazingly informative writeups. You are an asset to this forum.
I think you researched well and chose well. You did all you could as an informed patient.

Best of luck with your post-op recovery. I'll be cheering you on. Please do keep us updated if you have the time.

15

Ankle / Re: OATS Recovery Journal

« on: September 24, 2018, 09:41:42 AM »

something about dress shoes murders my ankle.. i always feel it the day after

i try to avoid dress shoes now. the best in terms of comfort and preserving my ankle has been Crocs