Is Fibrosis Forever? What a New Science Study Means for Endometriosis | ESSI

Key Takeaways

• A study published in Science on September 24, 2026 reversed established liver and lung fibrosis in mice by targeting a rare population of senescent, P-selectin-positive macrophages with drug-loaded nanoparticles¹.

• The broader lesson: fibrosis is not inert scar. Living cells keep it going, and in some settings it can regress when those cells are removed.

• Fibrosis is a core feature of endometriosis, and several ingredients of the Science model (senescent cells, disease-promoting macrophages and P-selectin) have already been described in endometriosis research.

• Nothing has been tested in endometriosis yet, and one laboratory study suggests fibrosis may partly hold endometriosis cells in check. Targeting it will need precision.

• For now, complete excision remains the only way to remove established fibrotic disease. This research points to possible future additions to surgery, not replacements for it.

If you have deep endometriosis, you may have heard your surgeon describe fibrosis, the dense scar tissue that forms in and around lesions. Endometriosis fibrosis is what makes a nodule hard, pale and woody. It fuses tissue planes that should separate cleanly, tethers an ovary to the pelvic sidewall or the bowel to the back of the uterus, and can narrow a ureter with a collar of scar.

For decades, this tissue has been treated as the end stage of the disease: something hormones can quiet but cannot undo, and something only surgery can remove. Underneath that view sits an assumption most doctors learned in training. Fibrosis is irreversible. If you have been told your pelvis is “frozen,” that can sound final.

A study published in Science on September 24, 2026, by a team at Memorial Sloan Kettering Cancer Center (MSK), adds to growing evidence that this assumption is too simple. In mice, the researchers reversed fibrosis that was already established in the liver and lung. They did it not by attacking the scar itself, but by removing a small population of cells that keep it going. The study says nothing yet about endometriosis. It does change the question worth asking about the scar tissue in your pelvis.

Why Fibrosis Matters So Much in Endometriosis

At ESSI, we approach endometriosis through the Pelvic Overlap Spectrum Syndrome (POSS): endometriosis and adenomyosis as co-anchors of a condition that can involve the bowel, bladder, pelvic nerves, ovaries and other systems at the same time. Fibrosis is one of the threads that ties those systems together. It is how a lesion becomes a problem for the organ next to it. Fibrosis tethers bowel, narrows ureters, distorts tubes and ovaries, surrounds nerves, and stiffens the uterine wall in the fibrotic form of adenomyosis.

This is not a side feature. In 2018, Viganò and colleagues argued that the definition of endometriosis should include its pro-fibrotic nature². A 2024 systematic review in Human Reproduction Update reached a similar conclusion. It described fibrosis and its main cellular driver, the myofibroblast, as central to the disease, with platelets and TGF-beta playing pivotal roles in the signals that drive it³.

The same review found that nerves and neuropeptides are closely associated with fibrosis in endometriotic lesions and are likely a cause of endometriosis-associated pain³. Its authors also suggested that comparing endometriosis with other fibrotic diseases, including liver cirrhosis, is a promising route to new treatments³.

Fibrosis also helps explain why endometriosis surgery tends to become more complex with time, a topic we covered in Is endometriosis progressive? Disease biology and timing of treatment. Hormonal treatments work by suppressing ovarian hormones and their effects on the disease. None was developed to remove fibrous tissue that is already there. As Viganò and colleagues put it, there is “a pressing need to identify effective pharmacological agents to block fibrosis”².

What the Science Study Did

The Cells Behind the Scar

Senescent cells have permanently stopped dividing but have not died. They stay metabolically active and release a mixture of inflammatory and tissue-remodeling signals, known as the senescence-associated secretory phenotype (SASP). They are sometimes nicknamed “zombie cells.”

Senescence is not simply harmful. In 2008, a team led by Scott Lowe, the senior author of the new study, showed that senescence of activated hepatic stellate cells, the liver’s main scar-producing cells, actually limits liver fibrosis⁴. A treatment that kills every senescent cell could therefore remove helpful cells along with harmful ones. The challenge is telling them apart.

The new study’s answer was a surface protein called P-selectin. The team found that P-selectin marks particular subsets of senescent-like cells in fibrotic tissues and in fibrotic tumors¹.

A Seaweed-Coated Delivery System

Working with Daniel Heller’s bioengineering laboratory, the researchers built nanoparticles coated with fucoidan, a sugar molecule from brown seaweed that naturally binds P-selectin. They loaded the particles with one of two drugs: navitoclax, which pushes senescent cells into programmed cell death, or dBET6, which leaves the cells alive but silences the inflammatory signals they release¹.

Both drugs had shown activity against senescent cells but caused toxicity when given freely throughout the body. Packaged in P-selectin-targeted particles, they kept their antifibrotic effect, and the mice were protected from the blood-count toxicities seen with the free drugs¹.

How the Nanotherapy Works

The mechanism operates across three continuous steps:

1. The Fibrotic Niche: A rare senescent macrophage carrying P-selectin signals scar-producing myofibroblasts and keeps protective T cells out of the tissue.

2. Targeted Delivery: A fucoidan-coated nanoparticle binds P-selectin and delivers navitoclax, which removes the cell, or dBET6, which silences its signals.

3. The Niche Remodels: Collagen and activated fibroblasts decline, and immune cells can move back into the tissue.

(Note: Demonstrated in mouse models of established liver and lung fibrosis where treatment began after fibrosis had formed; not yet tested in endometriosis. Based on Hinterleitner et al., Science 2026¹.)

Treating Fibrosis That Was Already There

This is the detail that matters most. The team did not use the treatment to prevent fibrosis. They induced liver fibrosis over six weeks and lung fibrosis over 28 days, and only then started treatment¹.

Both nanoparticle versions reduced collagen deposition and the number of activated, scar-producing fibroblasts. In the liver, blood flow through the portal vein and blood markers of liver injury also improved. The authors report that the particles reversed established fibrosis in both organs¹.

A Small Population with a Large Effect

When the researchers looked for the cells doing most of the work, they found that only 3% to 5% of cells in the fibrotic tissue were the senescent macrophages sustaining it⁵.

These specific macrophages carried both P-selectin and the hallmarks of senescence. They sat next to activated fibroblasts and blood vessels, and other immune cells such as T cells and B cells were largely excluded from their neighborhood¹. As co-first author Valentin Barthet described it, by sending out pro-fibrotic and immunosuppressive signals, “they essentially put up a wall”⁵.

In fibrotic liver and lung tumors in mice, removing or quieting these macrophages opened the tissue to immune cells and allowed checkpoint-inhibitor immunotherapy to shrink tumors that had previously resisted it¹,⁵. In human tissue, the team found a matching cell signature in fibrotic settings. In a group of lung cancer patients who received immunotherapy and chemotherapy before surgery, a higher abundance of these cells in the tumor predicted a poorer response¹.

The same harmful macrophages also turned up in a large database of immune-cell profiles from breast and colon cancer and from chronic inflammatory diseases such as osteoarthritis and rheumatoid arthritis.

What the Study Did Not Show

This is a mouse study of liver and lung. The human findings are observational: they show that these cells exist and track with worse outcomes, not that removing them helps people. The nanoparticles have not been given to patients, and MSK says it is seeking commercial partners to move the work toward clinical trials. The authors also note that remodeling the tumor environment on its own was not enough for durable tumor control without immunotherapy¹.

The Bigger Lesson: Fibrosis Is Maintained, Not Just Deposited

The most useful idea in this paper is not the nanoparticle. It is the demonstration that established fibrosis depends on ongoing signals from living cells. Take away the cells sending those signals, and the tissue can begin to remodel.

That idea has precedent in patients. In a five-year study of people with chronic hepatitis B treated with tenofovir, 74% of patients (71 of 96) who had cirrhosis at the start no longer had cirrhosis on repeat biopsy⁶. Removing the injury allowed even advanced scarring to regress.

In a mouse model of scleroderma, navitoclax, the same drug used in the Science study, reversed established skin fibrosis by triggering the death of myofibroblasts⁷.

“Irreversible” may have described the limits of our tools more than a law of biology.

How This Might Apply to Endometriosis

We want to be careful here. There are no data on this nanotherapy in endometriosis. But several pieces of the Science model are already present in endometriosis research, which is why we think the study deserves your attention.

Senescent Cells Are Present in Endometriotic Lesions

In a study of 27 patients undergoing surgery, deep endometriotic lesions showed a pattern consistent with cellular senescence when compared with the uterine lining: higher expression of the senescence marker p16INK4a in the secretory phase, lower lamin B1 in the proliferative phase, and higher IL-1 beta in both phases⁸. The same group later validated methods for mapping senescence markers across deep, superficial and ovarian lesions⁹. A 2026 study in Aging Cell went further, describing a senescence-driven subtype of endometriosis with more aggressive and immune-modulating features¹⁰.

Macrophages Can Drive or Restrain the Disease

Macrophages are central to endometriosis, and where they come from appears to matter. In a mouse model, macrophages that originated in the endometrium promoted lesion growth, while newly recruited, monocyte-derived peritoneal macrophages helped limit it¹¹. That is the same principle as the Science study: not all macrophages are harmful, and the goal is to remove the wrong ones while sparing the right ones.

P-Selectin Has Been on the Endometriosis Radar for a Decade

P-selectin is not new to our field. In 2015, Guo and colleagues proposed it as a potential therapeutic target for endometriosis¹². P-selectin is a classic marker of activated platelets, and platelets act as first responders to the repeated cycles of bleeding, injury and repair within lesions, where they help drive the transformation of cells into scar-producing myofibroblasts¹³. The Science study adds a different angle: P-selectin may also mark a harmful senescent macrophage state, and it can serve as a delivery address for drugs.

Endometriosis Fibrosis Can Be Modified, at Least in Primates

The most direct evidence that endometriosis-related fibrosis is not fixed comes from a primate study. In cynomolgus monkeys with surgically induced endometriosis, a long-acting antibody against IL-8 (AMY109) reduced nodular lesion volume and attenuated fibrosis, while fibrosis in untreated animals did not change¹⁴. AMY109 remains investigational.

A Necessary Caution: The Scar May Also Be Containing the Disease

One laboratory study tested navitoclax directly on stromal cells from deep endometriosis. It reduced collagen-producing myofibroblasts, but it increased the proliferation of ordinary fibroblasts, and the authors concluded that their findings do not support fibrosis as a therapeutic target in endometriosis¹⁵.

It was a cell-culture study without an animal model, but it raises a real possibility: in endometriosis, fibrosis may be both damage and containment. Dissolving scar around viable disease, without removing the disease, could in theory make things worse.

The Science paper points toward a more precise approach than simply killing scar-producing cells: target the specific cell state that sustains the fibrotic niche. Whether such a state exists in human endometriosis is a question that can be answered in the tissue already removed at surgery.

Where This Could Matter Someday

If a targeted antifibrotic approach eventually proves safe and effective in endometriosis, we see three places where it might fit. Each is still hypothetical:

• After complete excision, to reduce re-scarring, adhesion re-formation and recurrence in a pelvis that has just been operated on.

• Around nerves, where fibrosis and nerve involvement travel together and contribute to pain³.

• In the fibrotic form of adenomyosis, the other anchor of POSS, where a scarred uterine wall shapes both symptoms and uterus-sparing treatment planning.

In each case, the likely role is as an addition to surgery, not a replacement for it.

What This Does Not Change Today

This is not a reason to wait. When surgery is indicated, complete excision is the only way to remove established fibrotic disease.

• There is no approved or proven treatment that reverses fibrosis in endometriosis.

• Supplements marketed as “senolytics” have not been shown to reverse endometriosis or its fibrosis.

• Navitoclax is not approved for fibrosis or endometriosis, and given freely it causes significant side effects, including low platelet counts.

• Waiting for a future drug is not a reason to delay surgery that is otherwise indicated, particularly when the bowel, ureters or nerves are involved.

• Early diagnosis still matters. Fibrosis accumulates over time, and the best moment to deal with it is before it has reshaped the pelvis. Endometriosis MRI mapping can show where deep disease sits before any operation is planned.

The ESSI Perspective

For years, the working model was simple: hormones for active disease, surgery for fibrosis, and fibrosis as the point of no return. The Science study, together with the liver regression data and the primate endometriosis work, supports a more nuanced model. Fibrosis is a living process with a cellular engine. Some of that engine may be targetable. Some of it may be holding disease in check. Which is which will likely differ by organ, by lesion and by patient.

That is the kind of question POSS asks us to think about: not only where the disease is, but what it is doing to the tissues around it and how that changes over time. We will follow this line of research closely, and we will update you when there is evidence from endometriosis itself.

Frequently Asked Questions

Is endometriosis scar tissue permanent?

No medication has been shown to dissolve established fibrosis in human endometriosis, and hormonal treatments were not designed to do so. Research in other organs shows fibrosis can regress when the cells or injury sustaining it are removed. Whether the same is true in endometriosis has not yet been tested.

Should I delay surgery and wait for these treatments?

No. Any clinical use is likely years away, if it happens at all. When surgery is indicated, complete excision removes established fibrotic disease now, and delay can allow further involvement of the bowel, ureters or nerves.

Does hormonal therapy reverse fibrosis?

Hormonal treatments can reduce symptoms and suppress hormone-responsive disease activity, but they were not designed to remove fibrous tissue that is already established.

What is the difference between fibrosis and adhesions?

Fibrosis is scarring within and around endometriosis lesions, where collagen and myofibroblasts replace normal tissue. Adhesions are bands of scar tissue that join organs or surfaces that are normally separate. The two often occur together, and both can distort pelvic anatomy.

Fucoidan is sold as a supplement. Should I take it?

In the study, fucoidan was the coating that steered potent drugs to a specific group of cells. The study does not show that fucoidan supplements affect fibrosis, and they have not been shown to treat endometriosis.

Are senolytic supplements worth trying?

There is no clinical evidence that over-the-counter products marketed as senolytics reverse endometriosis or its fibrosis. Please discuss any supplement with your physician before starting it.

Evaluation and Surgical Guidance

If you have been told your pelvis is “frozen,” our surgical team can review your imaging and history and explain your options. Complete excision of deep endometriosis and uterine-sparing management of adenomyosis are planned around complete anatomical mapping.

Inquiries: internationalendo.com

Educational content. Not medical advice. Speak with your own specialist about your care.

About the author: Andrea Vidali, MD, is the founder and director of Endometriosis Surgical Specialists International (ESSI). Dr. Vidali is a fellowship-trained reproductive endocrinologist and reproductive immunologist and a high-volume robotic gynecologic surgeon.

References

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2. Viganò P, Candiani M, Monno A, Giacomini E, Vercellini P, Somigliana E. Time to redefine endometriosis including its pro-fibrotic nature. Hum Reprod. 2018;33(3):347–352. doi:10.1093/humrep/dex354

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5. Memorial Sloan Kettering Cancer Center. Using nanoparticles to target fibrosis in cancer and other diseases [news release]. September 24, 2026. https://www.mskcc.org/news/using-nanoparticles-to-target-fibrosis-in-cancer-and-other-diseases

6. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–475. doi:10.1016/S0140-6736(12)61425-1

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