Update: Stem Cells and Fat Grafting

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. 

Here are a few new items on stem cells and fat grafting I’ve come across recently. 

First are a couple of nice posts by fellow plastic surgeon/blogger Dr. Thomas Fiala, the Orlando plastic surgery blog who is attending The Aesthetic Meeting 2011 in Boston this week.

Live from Boston: Fat grafting controversies !!  (May 6, 2011)

……It's pretty clear that fat grafting works, and can be done safely. There seem to be two major methods that work……

One bit of consensus: if the breast was not pre-expanded, you can't expect to get more than 100 cc of fat to survive.

ASAPS 2011: Best of Hot Topics (May 9, 2011)

Here are my choices for the "Hot Topics" presented at the Boston ASAPS meeting:

1. "Stem Cell Facelift" - Dr. Peter Rubin reviewed the literature on the so-called Stem Cell facelift. It turns out that there really is no consistent technique for this method. Many advertised "stem cell facelifts" are simply regular facelifts with regular fat grafting and don't involve any extra stem-cell work at all. Furthermore, to date, there is NO DATA that this technique is superior to facelift with standard fat grafting. Summary: as of today, the stem cell facelift can either be considered unproven and under development, or if you are a little more cynical, it might just be "marketing hype".

The review by Rubin was highlighted in a press release:   ASAPS and ASPS Issue Joint Position Statement on Stem Cells and Fat Grafting on Monday, May 9, 2011.

….. Based on the current state of knowledge, the task force made the following recommendations to ASAPS/ASPS members and their patients:

•     Terms such as "stem cell therapy" or “stem cell procedure” should be reserved to describe those treatments or techniques where the collection, concentration, manipulation, and therapeutic action of the stem cells is the primary goal, rather than a passive result, of the treatment. For example, standard fat grafting procedures that do transfer some stem cells naturally present within the tissue should be described as fat grafting procedures, not stem cell procedures.
•     The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence at this time.
•     While stem cell therapies have the potential to be beneficial for a variety of medical applications, a substantial body of clinical data to assess plastic surgery applications still needs to be collected. Until further evidence is available, stem cell therapies in aesthetic and reconstructive surgery should be conducted within clinical studies under Institutional Review Board approval, including compliance with all guidelines for human medical studies.  ………….

And the last item comes from the PRSonally Speaking Blog:  Articles of Interest Sneak Peak: Breast fat grafting with platelet-rich plasma: a comparative clinical study and current state of art.  It highlights the abstract of an article which will be published in the PRS journal in June 2011.

The role of Platelet-Rich Plasma (PRP) in enhancing fat grafts take is attracting the scientific community. However, there is a lack of clinical series on the matter.

The aim of this paper is to report Authors' experience in breast fat graft with and without PRP and to investigate the state-of-art on adipose tissue PRP enrichment……

Conclusion: In Authors' retrospective analysis no effect of PRP was seen in enhancing fat graft take when compared to Coleman fat graft. Further research and prospective clinical studies are strongly needed to understand the role of PRP, if any, in fat grafting.

Facing Monday

Updated 3/2017-- photos and all links removed as many are no longer active and it was easier than checking each one.

Last Monday was reported to be the saddest day of this year.   So to help you and I face Monday and the beginning of a new week, in case you missed these stories…..

Roger Ebert has written in his Chicago Sun Times blog of how he will once again be “Leading with my chin.” 

………..That was the beginning of a two-year process that has now resulted with my coming into possession of a silicone prosthesis. Dr. Reisberg brought in David Rotter, also from the University of Illinois, and he involved Julie Jordan Brown, a Milwaukee artist and anaplastologist. Working from molds, they created a prototype prosthesis and sculpted it carefully to more closely resemble what had been there before. This device would fit over my lower face and neck and, colored to match my skin, would pass muster at a certain distance……….

He will wear the facial prosthetic on his new show set to debuted Friday January 21, 2011:   Ebert Presents at the Movies.  He speaks using his voice through his laptop.

…….

Last week, we heard the voice of a woman who is only the second person to receive a larynx transplant.   The 52 yo California woman’s surgery was done by a team of surgeons at UC Davis Medical Center.

From this article by Aaron Saenz: Woman Speaks With Her Own Voice After Larynx Transplant (video) comes the reminder that just last year a 10 year old boy had a new trachea made from his own stem cells.

So is this surgery simply a fluke? …... According to Paolo Macchiarini, one of the surgeons involved, “Not only is it highly relevant for future transplants, it offers us insights that may one day lead to using stem cells to repair the voicebox and surrounding areas in the throat.”

When it comes to stem cells and the throat, Macchiarini knows what he’s talking about. Last year he was the leader of a team that grew a new trachea in a 10 year old boy using the child’s own stem cells. As he stated in regards to the Jensen case, “Being able to restore nerves and reconnect blood vessels in and around the larynx and trachea, and have it all work, was a real test.” Perhaps this most recent operation will lead to further remarkable work from Macchiarini in the near future.

 

Related posts

First Full Face Transplant Done! (July 12, 2010)

Facial Prosthetics Restores Face (August 5, 2010)

Double Hand Transplant on Twitter (August 26, 2010)

 

 

REFERENCE

Laryngeal Transplantation and 40-Month Follow-up; Marshall Strome, M.D., Jeannine Stein, M.D., Ramon Esclamado, M.D., Douglas Hicks, Ph.D., Robert R. Lorenz, M.D., William Braun, M.D., Randall Yetman, M.D., Isaac Eliachar, M.D., and James Mayes, M.D.; N Engl J Med 2001; 344:1676-1679

Risks of Fat Grafting in Breast Cancer Patients

Updated 3/2017-- all links (except to my own posts) removed as many are no longer active and it was easier than checking each one.

Fat grafting as a means of either (cosmetically) enlarging breasts or (reconstructively) correcting defects / asymmetries after breast cancer surgery/radiation therapy has been gaining ground as an acceptable method in the past few years.  True, much debate is still occurring but research is being encouraged to answer questions regarding safety (short and long-term) and efficacy.

The two articles (full references below) from researchers at the University of Pittsburgh School of Medicine suggests that it is NOT safe to use adipose-derived stem cells (ADSC) that may be part of fat grafting in any patient with active tumor cells. 

From the first article’s abstract (bold emphasis is mine):

Adipose-derived stem cells (ASCs) have been proposed to stabilize autologous fat grafts for regenerative therapy, but their safety is unknown in the setting of reconstructive surgery after mastectomy. ….

Here, we ask whether ASC promote the in vitro growth and in vivo tumorigenesis of metastatic breast cancer clinical isolates. Metastatic pleural effusion (MPE) cells were used for coculture experiments. ASC enhanced the proliferation of MPE cells in vitro (5.1-fold). ……… The secretome profile of ASC resembled that reported for MSC, but included adipose-associated adipsin and the hormone leptin, shown to promote breast cancer growth. Our data indicate that ASC enhance the growth of active, but not resting tumor cells. Thus, reconstructive therapy utilizing ASC-augmented whole fat should be postponed until there is no evidence of active disease.

From the second article’s abstract (bold emphasis is mine):

There is often a pressing need for reconstruction after cancer surgery. Regenerative therapy holds the promise of more natural and esthetic functional tissue. In the case of breast reconstruction postmastectomy, volume retention problems associated with autologous fat transfer could be ameliorated by augmentation with cells capable mediating rapid vascularization of the graft. …..

. Available evidence from case reports, cell lines, and clinical isolates favors the interpretation that regenerating tissue promotes the growth of active, high-grade tumor. In contrast, dormant cancer cells do not appear to be activated by the complex signals accompanying wound healing and tissue regeneration, suggesting that engineered tissue reconstruction should be deferred until cancer remission has been firmly established.

The early research suggest that fat grafting as a reconstructive tool in breast cancer survivors is safe (non-tumor causing) as long as care is taken to be sure any remaining tumor cells are dormant and non-active.

It must be remembered that fat grafting is a surgical procedure and as such is not risk free.  All surgical procedures carry the risks of infection, bleeding, etc.  The fifth reference below reminds us that fat grafting is not always a simple, benign procedure.

Autologous fat grafting to the breast for breast reconstruction and cosmetic breast augmentation has gained much attention recently. However, its efficacy and the severities of its associated complications are of concern. The authors experienced one case of multiple breast abscesses after augmentation mammoplasty by autologous fat grafting. ………. 

Immediate complications such as edema, hematoma, and infection require serious consideration after autologous fat grafting in the breast. In particular, infection probably is the most serious complication because the volume of the fat injected is large and can induce systemic infections such as sepsis and distort the contours of the breast. To avoid such infections, systemic and multicenter studies are required to determine how fat grafting should be performed to minimize the risks of fat necrosis and infection.

REFERENCES

Regenerative Therapy and Cancer: In Vitro and In Vivo Studies of the Interaction Between Adipose-Derived Stem Cells and Breast Cancer Cells from Clinical Isolates; Ludovic Zimmerlin, Albert D. Donnenberg, J. Peter Rubin, Per Basse, Rodney J. Landreneau, Vera S. Donnenberg; Tissue Engineering Part A. September 2010, ahead of print.

Regenerative Therapy After Cancer: What Are the Risks?; Vera S. Donnenberg, Ludovic Zimmerlin, Joseph Peter Rubin, Albert D. Donnenberg; Tissue Engineering Part B: Reviews. November 2010, ahead of print.

Fat Grafting to the Breast Revisited: Safety and Efficacy; Coleman, Sydney R.; Saboeiro, Alesia P.; Plastic & Reconstructive Surgery. 119(3):775-785, March 2007; doi: 10.1097/01.prs.0000252001.59162.c9
Autologous Fat Grafting to the Reconstructed Breast: The Management of Acquired Contour Deformities; Kanchwala, Suhail K.; Glatt, Brian S.; Conant, Emily F.; Bucky, Louis P.; Plastic & Reconstructive Surgery. 124(2):409-418, August 2009; doi: 10.1097/PRS.0b013e3181aeeadd
Sepsis With Multiple Abscesses After Massive Autologous Fat Grafting for Augmentation Mammoplasty: A Case Report; Keu Sung Lee, Seung Jo Seo, Myong Chul Park, Dong Ha Park, Chee Sun Kim, Young Moon Yoo and ll Jae Lee; Aesthetic Plastic Surgery, November 2010; DOI: 10.1007/s00266-010-9605-8

Stem Cells

Updated 3/2017-- all links (except to my own posts) removed as many are no longer active and it was easier than checking each one.

The October issue of the Plastic and Reconstructive Surgery Journal has a nice review article of stem cells (bold emphasis is mine).  The article gives an overview of current advancements in the field of stem cell research, as well as perspectives for future clinical applications.

Stem cells are defined by their capacity to both self-renew and differentiate into multiple cell lines. Traditionally, they have been divided into two main groups based on their potential to differentiate. Pluripotent stem cells (embryonic) can differentiate into every cell of the body, whereas multipotent stem cells (adult) can differentiate into multiple, but not all, cell lineages.

In addition to the traditional stem cell classification, a new class of stem cells has recently been described—induced pluripotent stem cells—which are derived from genetically reprogrammed adult cells. These diverse cell populations will provide researchers and clinicians with an expanded armamentarium to treat diseased and dysfunctional organs.

Embryonic stem cells

• are derived from the inner cell mass of the blastocyst and have the capacity to differentiate into all tissues of the body.
• at least 225 human embryonic stem cell lines have been generated by researchers
• the pluripotentiality and unlimited ability for self-renewal that make embryonic stem cells attractive for cell replacement therapy also simultaneously translates into unregulated differentiation and formation of teratomas and teratocarcinomas, especially in undifferentiated states
• significant political and ethical hurdles that hinder further investigations of human embryonic stem cells

Adult stem cells

1. avoid the ethical concerns regarding fetal tissue harvest
2. well-studied adult stem cell population includes mesenchymal stem cells
3. Mesenchymal stem cells have been isolated from bone marrow, umbilical cord blood, and adipose tissue.
4. Adipose tissue–derived stem cells can be readily harvested during a minor liposuction procedure under local anesthesia.

Induced pluripotent stem cells

1. Takahashi and Yamanaka published a landmark article in 2006 that defined a specific set of transcription factors capable of reverting differentiated cells back into a pluripotent state, thus creating “induced” pluripotent stem cells.
2. It is widely accepted that mouse and human induced pluripotent stem cells closely resemble molecular and developmental features of blastocyst-derived embryonic stem cells

While the clinical potential for stem cell use is huge as noted in the article

Stem cell–based clinical trials are still in the early stages of development. In a preliminary case study, three patients were treated with autologous bone marrow stem cells seeded onto porous ceramic scaffolds for limb cortical defects ranging from 4 to 7 cm.  ………

In another case report, a 7-year-old girl with a critical-sized calvarial defect was successfully treated with cancellous iliac bone grafts in combination with autologous adipose tissue–derived stem cells.

In a case series, 20 patients with severe symptoms or irreversible functional skin damage due to radiotherapy were treated with autologous adipose tissue–derived stem cells delivered by computer-assisted injections.  …….

Interestingly, the first clinical phase I trial for utilizing adipose tissue–derived stem cells was carried out in patients with Crohn's disease. …..
In another phase I clinical trial, eight patients with Duchenne disease were treated with myogenic (muscle-derived CD133⁺) stem cells. ….

there is abuse of the term stem cell.  Stem cells facelifts are a marketing scheme (IMHO) which are promising results that haven’t been studied.

Stem Cell Face-Lifts?
Stem Cell Facelift: Fact or fiction?
The Newest Untested Fad:  Stem-Cell Facelifts
and from Dr. Thomas Fiala’s this blog post The "Stem Cell" facelift

But so far, we have no evidence - zip, zilch, nada - that there is any actual regenerative effect on skin when the turbo-charged fat is added to the face. We know you get more volume in the treated areas, so the treatment could be useful for those with a volume-depleted area, or those who want fuller cheeks - but that's about it.

Furthermore, under FDA rules, when stem cells get involved with fat transfers, the procedure falls under a whole new set of regulations. The fat and stem cell combo is now seen as a "biologic agent" by the FDA, and regulated as a drug. In the eyes of the FDA, stem cells and fat represent a non-approved drug. Investigational, yes - approved, no.

Interestingly, one of the spin-offs of this change to drug status is a change in whether physicians can advertise this process. They are no longer just advertising a procedure (the stem cell facelift), but they are doing direct-to-consumer marketing for a drug (the fat and stem-cell mixture) which has not yet been cleared by the FDA. And it's illegal to promote non-approved drugs.

Dr. Barry Eppley disagrees with the above stance in his post:  Stem Cell Facelifts - Science or Science Fiction?

Conversely, the hopeful part of a Stem Cell Facelift is that it is a perfectly natural procedure that has no harmful effects, an almost organic procedure if you will. It is all the patient’s own tissues and may exemplify the appealing concept of ‘heal thyself’. Because one’s own cells are being used (recycled?), it is not a procedure that requires FDA approval or that of any governing medical organization. (so don’t be misled that it is an FDA-approved procedure or technique) At the worst, one gets the benefit of fat grafting whether the stem cells really become alive or not. And the use of fat grafts to the face with our current appreciation of what happens as our face ages is a proven benefit.

However, in checking the FDA’s own website, I find that I would disagree with Dr. Eppley and agree with Dr. Fiala:  What are stem cells? How are they regulated?

Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require FDA approval before they can be marketed. At this time, there are no licensed stem cell treatments.

REFERENCES

Stem Cells; Behr, Björn; Ko, Sae Hee; Wong, Victor W.; Gurtner, Geoffrey C.; Longaker, Michael T.; Plastic & Reconstructive Surgery 126(4):1163-1171, October 2010; doi: 10.1097/PRS.0b013e3181ea42bb

Stem Cell Face-Lifts?

Updated 3/2017--  all links (except to my own posts) removed as many are no longer active and it was easier than checking each one.

It’s been almost a month since the LA Times ran the article by Chris Woolston:  The Healthy Skeptic: Stem cell face-lifts on unproven ground.  It’s well written and presents a fairly balanced view.  While I am a fan of stem cell research, I think the “claims” are often put ahead of the science.  This is one of those times.  I can’t find any decent articles to support the claims of the plastic surgeons doing “stem cell face-lifts.”

My view is echoed in the article (bold emphasis is mine):

Rubin says he's excited about the potential of stem cells in the cosmetic field and beyond. Still, he adds, there are many unanswered questions about the cosmetic use of stem cells, and anyone who claims to have already mastered the technique is jumping the gun. As Rubin puts it, "Claims are being made that are not supported by the evidence."

While researchers in Asia, Italy, Israel and elsewhere are reporting decent cosmetic results with injections of stem cell-enriched fat, Rubin says that nobody really knows how the stem cells themselves are behaving. He points out that fat injections alone can improve a person's appearance, no stem cells needed.

Rubin believes it's possible that injected stem cells could create new collagen and blood vessels — as they have been shown to do in animals studies — but such results have never been proved in humans. And, he adds, the long-term effects of the procedures are an open question.

Stem cell face-lifts could someday offer real advances, says Dr. Michael McGuire, president of the American Society of Plastic Surgeons and a clinical associate professor of surgery at UCLA. But he believes that scientists are still at least 10 years away from reliably harnessing stem cells to create new collagen and younger-looking skin. Until then, promises of a quick stem cell face-lift are a "scam," he says.

The American Society for Aesthetic Plastic Surgery (ASAPS) issued a statement two weeks after the article first appeared --Stem cell therapy 'could offer women natural breast enhancement from stomach fat'

“Procedures with no solid science behind them, stem cells included, give unproven hope to patients and the marketing of them brings dishonor to our entire specialty,” said Felmont Eaves, III, MD of Charlotte, NC, President of ASAPS.  The Aesthetic Society is working together with the other core societies to address this through an evidence based medicine program that will rate any procedure or device on the legitimacy of the scientific evidence behind it.  This program is in its development stage and will be available to the public within the next 12 months”.

“The use of ‘stem cells’ in advertising for cosmetic surgical applications is a global problem," says Doug Sipp, Head of the Science Policy and Ethics Study Unit at the Center for Developmental Biology of RIKEN in Kobe, Japan, who monitors supposed stem cell treatment claims worldwide in all different specialties.  "There have been many cosmetics, nutraceuticals, and device makers who claim either to use stem cells in their products, or to use ingredients that activate the customer’s own stem cells. To the best of my knowledge, none of these has a basis in scientific evidence."

Marketing.  That seems to be the issue here.  And there is much money to be made in promises that may or may not be kept with the use of stem cells.  From the LA Times article:

Stem cell face-lifts: A Sept. 13 Health section story assessing stem cell face-lifts offered by two Beverly Hills doctors said that Dr. Nathan Newman charges between $5,500 and $9,500 for the procedure and Dr. Richard Ellenbogen charges $15,000 to $25,000. The story should have noted that Ellenbogen often performs a surgical face-lift along with his injection of stem cells. —

Stem Cells in Breast Augmentation?

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. and it was easier than checking each one.


There is a short article, Using Stem Cells in Breast Augmentation, in the January 2010 issue of the PSP Newsletter.  It is more an interview of Todd Malan, MD by Connie Jennings than a scientific article (and that’s okay). 

It is an interesting read which includes some of the history of fat grafting for breast augmentation, particularly in the United States but also world wide.  It will be interesting to watch as this procedure/method evolves.  I hope it will be done with scientific protocol that really looks at how it works, if it works, the risks, etc.

Dr. Malan quotes the costs:

Cost wise, liposuction with fat transfer to the breasts is only about $5,000 over the cost of just liposuction.  It is comparable in cost to a breast augmentation with implants and liposuction.

However, adding stem cells to the mix adds an additional $5,000 to the procedure.  This is because the procedure for processing and extraction of the stem cells is very time consuming and expensive.  The disposables that are required for the 3-hour procedure cost around $2,800.

The automated processing is faster and cheaper than the manual extractions, which are popular in Japan and Korea.  Using the latest automated devices saves time and money, but is still more costly than implants.  However, if you look at the lifetime cost of implants based on published statistics on complications and reoperation, then fat transfer is actually less expensive.

From the UK Times article last March:

A STEM cell therapy offering “natural” breast enlargement is to be made available to British women for the first time.

The treatment could boost cup size while reducing stomach fat. It involves extracting stem cells from spare fat on the stomach or thighs and growing them in a woman’s breasts. An increase of one cup size is likely, with the potential for larger gains as the technique improves.

A trial has already started in Britain to use stem cells to repair the breasts of women who have had cancerous lumps removed. A separate project is understood to be the first in Britain to use the new technique on healthy women seeking breast enlargement.

Professor Kefah Mokbel, a consultant breast surgeon at the London Breast Institute at the Princess Grace hospital, who is in charge of the project, will treat 10 patients from May. He predicts private patients will be able to pay for the procedure within six months at a cost of about £6,500.

Other related articles:

Breast Augmentation Via Fat Grafting:  The History and the Controversy  by Sydney R. Coleman, MD; PSP January 2008

Stem Cells May Fix Breast Defects; PSP December 2007

Stem Cells to Grow Bigger Breasts by Jeffrey Frenzen; PSP April 2009

Stem cells to grow bigger breasts; (UK) Times Online article, March 2009

Previous related blog posts:

Update on Breast Augmentation Using Fat Injections (November 2, 2009)

ASPS Task Force Updates Position on Fat Grafting (August 13, 2009)

Recent NPR Stories on Plastic Surgery (June 3, 2009)
Complications After Autologous Fat Injections to the Breast – an Article Review (April 2, 2009)

Fat Injections for Breast Augmentation (November 6, 2008)

Bioactive Sutures

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. and it was easier than checking each one.

H/T to MedGadget who’s post introduced me to “bioactive sutures.”  What a great idea by the Johns Hopkins biomedical engineering students! 

……have demonstrated a practical way to embed a patient’s own adult stem cells in the surgical thread that doctors use to repair serious orthopedic injuries such as ruptured tendons. The goal, the students said, is to enhance healing and reduce the likelihood of re-injury without changing the surgical procedure itself.

The project team of 10 undergraduates focused on Achilles tendon injuries which require repair in approximately 46,000 people in the United States every year.   The surgery may fail in as many as 20%.  Recovery can take up to a year even with successful surgery.  If this new suture speeds healing and lowers failure rates – what potential! 

At the site of the injury, the stem cells are expected to reduce inflammation and release growth factor proteins that speed up the healing, enhancing the prospects for a full recovery and reducing the likelihood of re-injury. The team’s preliminary experiments in an animal model have yielded promising results, indicating that the stem cells attached to the sutures can survive the surgical process and retain the ability to turn into replacement tissue, such as tendon or cartilage……………

As envisioned by the company and the students, a doctor would withdraw bone marrow containing stem cells from a patient’s hip while the patient was under anesthesia. The stem cells would then be embedded in the novel suture through a quick and easily performed proprietary process. The surgeon would then stitch together the ruptured Achilles tendon or other injury in the conventional manner but using the sutures embedded with stem cells.