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25.6.2025

Adipose-derived stem cells remember obesity – anti-inflammatory capacity restored only years after weight loss

 


Doctoral Researcher Amna Adnan investigated the impact of obesity on the immunomodulatory and angiogenic potential of adipose-derived stem cells. Where previous studies have relied on animal models and multiple donors, Adnan harvested cells longitudinally from the same individual. The research was conducted at the Adult Stem Cell Group at Tampere University.
Photo: Jonne Renvall/Tampere University

In medically indicated weight loss, attention is typically focused on the associated health benefits. However, recent research findings suggest that recovery from obesity-induced systemic inflammation may take several years.

Amna Adnan’s new study sheds light on how weight loss influences the functional characteristics of adipose stem cells at the cellular level. She examined adipose-derived stem cells harvested from the same donor before and after bariatric surgery and subsequent weight loss.

Bariatric surgery involves reducing or bypassing the stomach to limit food intake, with the aim of achieving weight loss and alleviating obesity-related conditions such as type 2 diabetes and cardiovascular disease.

Adipose stem cells are an efficient form of regenerative therapies. Their properties facilitate tissue repair, suppress immune rejection in grafts and promote the regeneration of tissues. Their therapeutic potential is being explored in the treatment of osteoarthritis, cardiovascular diseases, chronic wounds and Crohn’s disease.

Adipose stem cells can be harvested, among other things, via liposuction with minimal risk to the donor. However, donor-specific factors – such as body mass index and weight loss history – affect their suitability for stem cell-based therapies.

Previous studies have shown that obesity impairs the anti-inflammatory functions of adipose stem cells. Adnan hypothesised that these functions would be restored following weight loss, but the findings did not support this assumption.

The analysis of tissue biopsies and plasma samples revealed a reduction in systemic inflammation after weight loss. However, the regulatory mechanisms governing inflammatory responses in adipose stem cells had not returned to baseline at the cellular level.

“These results have reshaped our understanding of adipose stem cell behaviour following weight loss. Even though bariatric surgery improves general health, the functional recovery of adipose stem cells remains incomplete even two to three years after the intervention. This means that individuals who have undergone significant weight loss may not be suitable donors for cell therapies aimed at suppressing inflammatory responses,” Adnan explains.

Led by Professor Susanna Miettinen, the Adult Stem Cell Group is developing a tissue culture model derived from adipose tissue. The aim is to investigate the functional differences between healthy and diseased adipose tissue, and to support drug testing and the advancement of personalised medicine. In an upcoming research project, adipose-derived stem cells and vascular endothelial cells will be cultured on a three-dimensional tissue chip to study their angiogenic potential. The study will utilise stem cells obtained from donors with normal weight, overweight and morbid obesity. The first results are expected in autumn 2026.

The article Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study was published in Stem Cells International on 13 May 2025. Read the article online

Further information

Amna Adnan
amna.adnan@tuni.fi
+358504799946

Adult Stem Cell Group

13.1.2025

Open positions in Adult Stem Cell group and CoEBoC!

Great summer job opportunities for students!

Research assistant in CoEBoC: Apply here!

Application deadline 2.2.2025.

 

Positions in Adult Stem Cell group:

Doctoral researcher: Apply here

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Postdoctoral research fellow: Apply here

Application deadline 20.1.2025.

10.10.2024

Researchers succeed in creating two interconnected vascular networks

“The generation of two distinct, interconnected 3D microvascular networks marks a significant step forward in biomedical research”, says doctoral researcher Alma Yrjänäinen.Photo: Jonne Renvall / Tampere University

Researchers at Tampere University have developed a groundbreaking cell culture platform that enables the formation of two distinct but interconnected vascular networks. Their breakthrough holds tremendous promise for advancing biomedical research. Organ-on-chips are microfluidic cell cultures that replicate human physiology, significantly reducing the costs of drug development, minimising the need for animal testing and enabling personalised treatment.

Researchers from the Faculty of Medicine and Health Technology (MET) at Tampere University have successfully created a cell culture platform that allows two cultivated vascular networks to interconnect. The blood vessels in these networks are equivalent to human capillaries in size and structure, facilitating the study of human capillary networks in a laboratory setting. Their research paper was published in Scientific Reports on 2 October 2024.

“The generation of two distinct, interconnected 3D microvascular networks marks a significant step forward in our research. Now we can incorporate cells found in different types of tissue around these interconnected vascular networks – such as hepatocytes from liver tissue and adipocytes from fat tissue – to study cellular interactions in vascularized tissues,” says Alma Yrjänäinen. She is working on her PhD within the Centre of Excellence in Body-on-Chip Research at Tampere University.

Organ-on-chip (OoC) technology combines microfabrication techniques and cell biology to facilitate the study of tissue functions. OoCs replicate the complex microenvironment of human tissue by incorporating either gravity-driven or pump-assisted fluid flow through miniaturised tissue, mimicking the natural forces of blood flow. Neurons and blood vessels can also be integrated into these models.

OoCs can substantially reduce the costs of drug discovery, with experts estimating a potential reduction of up to 25%. National healthcare systems could also benefit from the adoption of OoCs. However, further progress is needed before these visions become a reality.

“Imagine that in the future, a single blood sample could unlock a personalised treatment for your hypertension. Stem cells derived from your blood could be used to create a vascular network in a laboratory setting. This network could then be used to test which hypertension drugs available on the market would be most suitable for your cells, helping to avoid drugs that would be ineffective or even harmful to you,” Yrjänäinen says.

 

 

Leading OoC researchers to convene in Tampere in October

Finnish and international experts in Organ-on-Chip (OoC) technology will gather for the Finnish Organ-on-Chip (FIN OoC) meeting on 23–24 October 2024. The event will also delve into the ethical dimensions of OoC technology, guided by Jeremy Sugarman, an internationally recognised authority in biomedical ethics. The event is organised by the Centre of Excellence in Body-on-Chip Research on the Kauppi campus of Tampere University.

Read more about FIN OoC 2024 and see the full programme

What is organ-on-chip (OoC) technology?

  • OoC technology is a multidisciplinary field of research that emerged in the 2010s and aims to create models that mimic specific human tissues.
  • Due to advancements in stem cell technology, isolating cells directly from a patient’s heart is no longer required to create a personalised heart model. Instead, these models can now be engineered from easily harvested blood cells, which are first reprogrammed into stem cells and then into heart cells.
  • OoC models are used to study tissue-specific diseases, improve treatments, analyse drug responses and discover new therapies.
  • OoC technology also helps to reduce or replace the need for animal testing.

Helsingin Sanomat 30.10.2021:

Tampereen yliopistossa onnistuttiin tulostamaan leukaluun mallikappale elävistä soluista

Linkki Helsingin Sanomien uutiseen:
https://www.hs.fi/tiede/art-2000008371579.html

New publication: Donor’s weight affects adipose stromal/stem cell properties – Implications for cell therapies

Adipose stromal/stem cells (ASC) are attractive candidates for many cell therapy applications. Several studies have shown that donor’s overweight or obesity affect ASCs’ properties. Previous studies suggest that ASC from overweight or obese donors are not suitable e.g., for cell therapies for inflammatory diseases or for bone tissue engineering applications.

Now, a publication studying the effect of ASC donor weight has been published by CoeBoC’s Adult Stem Cell group in collaboration with Obesity research unit in University of Helsinki. The aim of the study was to evaluate the effect of donor weight on ASCs’ properties utilizing cells isolated from monozygotic weight-discordant (WD) twin pairs while controlling the genetic variation between leaner and heavier groups. Results showed that weight did not affect the proliferation, immunogenicity, osteogenic differentiation, or mesenchymal stem cell-like immunophenotype. However, higher weight of the WD twin increased adipogenic differentiation, expression of inflammation marker TNF and immunosuppression capacity and decreased angiogenic potential and expression of pericyte marker CD146 compared with leaner co-twin.

Based on our results, even a small difference in body mass index (BMI) in metabolically healthy donors affects some of the ASC characteristics. Regarding to future cell therapies, the weight of the donor should be considered as a selection criterion, especially for allogeneic cell therapies utilizing ASC.

Moreover, the results can be utilized in the next steps in the development of obesity-in-chip in Centre of Excellence, CoE-BoC (https://research.tuni.fi/coeboc/).

The research was funded by Business Finland, Academy of Finland, Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, Finnish Cultural Foundation and Tampere University Graduate School for Medicine and Life Sciences, Helsinki University Hospital funds, the Finnish Diabetes Research Foundation, the Orion Foundation, the Paulo Foundation, the Finnish Medical Foundation and the Maud Kuistila Foundation, the Gyllenberg Foundation, the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the University of Helsinki and the Government Research Funds through Helsinki University Hospital.

Juntunen M, Heinonen S, Huhtala H, Rissanen A, Kaprio J, Kuismanen K, Pietiläinen KH, Miettinen S, Patrikoski M. Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs. Stem Cell Res Ther. 2021 Sep 26;12(1):516. doi: 10.1186/s13287-021-02587-0.

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Alma has pitched her PhD work in 3-minute thesis (3MT) pitching competition organized by Tampere University. See the video of her pitch in here. She has also been qualified for Millennium Pitching Competition.

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