Autologous cell therapies

Autologous cell therapies make use of the natural endogenous mechanisms for the regeneration and healing of injured tissue. The body’s response to an injury is a complex healing cascade in order to heal the wound as quickly as possible. To understand how this regeneration process works, let us take a look to the cellular level.

THE PHYSIOLOGICAL REGENERATION PROCESS

Histologically, three types of cells can be discerned in the blood:

  1. Erythrocytes responsible for the transportation of oxygen and carbon dioxide,
  2. leukocytes which divide up into different types
    and regulate the immune defense,
  3. as well as thrombocytes, also referred to as blood platelets.

Platelets are responsible for hemostasis, and mediate the first phases of wound healing. In this phase, platelets aggregate and form the blood clot. In addition, growth factors are released by degranulation of thrombocytes.

The release of cellular growth factors supports healing by

  • Attracting undifferentiated cells to the site of the injury (chemoattraction and migration) and by stimulating mitosis of undifferentiated cells (proliferation)
  • Suppressing cytokine release, thus moderating inflammatory and anti-inflammatory reactions
  • Attracting macrophages for the improvement of tissue healing and regeneration
  • Supporting capillary growth and accelerating epithelization

Leukocytes form several cytokines, referred to as interleukins. They mediate between leukocytes and play an important role in immune defense.

Excursus Exosomes: the secret drivers behind regenerative medicine

The exact functional mechanisms in regenerative medicine have not yet been conclusively researched. However, some important processes are already nderstood. Exosomes play a pivotal role in tissue repair and regeneration, acting as critical mediators of intercellular communication. These nano-sized extracellular vesicles (30–150 nm) are secreted by nearly all cell types and contain a cargo of proteins, lipids, and nucleic acids (especially microRNAs) that can influence the behavior of recipient cells

Accelerated regeneration and tissue repair – mechanisms of action

Exosomes are thus able to control and influence a multitude of vital processes in the body:

  • Immune modulation
  • Modulation of inflammation
  • Paracrine signaling
  • Promotion of angiogenesis
  • Remodeling of extracellular matrix (ECM)

AUTOLOGOUS CELL THERAPIES – THE BODY´S OWN HEALING IMPULSE

Autologous cell therapies use exactly these processes of the natural healing cascade – the body´s complex response to an injury. They contain growth factors, anti-inflammatory cytokines, exosomes or stem cells in concentrated form, for example. After injection to the defect, they assist the body in a natural way with their regenerative and healing properties.

The following autologous preparations can be distinguished:

PLATELET-RICH PLASMA: NOT ALL PRP IS THE SAME

PRP principles of preparation
The starting point is always the patient’s venous whole blood. Centrifugation of the blood sample separates the cellular fractions of the blood. Depending on the therapeutic goal, different cellular components are separated; moreover, different concentrations of these components are possible.1

PRPs can be activated before application by adding activating substances (e.g. calcium gluconate or autologous thrombin).2 Since platelets get activated once they come in contact with soft tissue and collagen, activation is not a necessity

Leukocyte-poor variants

Single-Spin PRP – low concentration PRP

First centrifugation

Double-Spin PRP – highly concentrated PRP (= APC)

Second centrifugation

Leukocyte-rich variants

First centrifugation

Second centrifugation

Leukocytes = white blood cells (WBC)

Thrombocytes = blood platelets

Erythrocytes = red blood cells (RBC)

So-called “single-spin” PRPs have a low concentration because they contain the full platelet-poor plasma (PPP) fraction.

If the PRP is injected shortly after preparation, the use of an anticoagulant can be dispensed with.

Single-Spin PRP can be concentrated by a second centrifugation – depending on the therapy goal in the leukocyte-poor or in the leukocyte-rich variant. Due to the slightly longer preparation time, the use of an anticoagulant is recommended. The platelets are then dissolved in a small amount of plasma. The number of platelets per ml is higher than with single-spin PRPs: Autologous Platelet Concentrate (APC).

(1) Mazzocca AD et al (2012): Platelet-rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am 94(4):308-316.
(2) Dhillon RS et al (2012) Platelet-rich plasma therapy-future or trend? Arthritis Res Ther 14(4):219.

IMPACT PRP Set – Without anticoagulant for the preparation of a “single-spin” PRP

Two PRP programs are present on the IMPACT platform:

Concentration vs. whole blood1 Yield
Cell Types Platelets Leukocytes Erythrocytes Platelets
rPRP 2-3 x <0,9 x <0,15 x 95%
wPRP 2-3 x <0,2 x <0,01 x 92%

rPRP “Red” PRP: Leukocyte-rich, erythrocyte-poor
wPRP “White” PRP: Leukocyte-poor, erythrocyte-free

IMPACT PRP is a once centrifuged, not further concentrated PRP, which contains the full platelet-free plasma fraction. IMPACT PRP has been developed in such a way that the short and gentle centrifugation activates the platelets only slightly.

¹ Serum concentrations: TU Munich, Chair of Medical Technology

IMPACT APC Set – With anticoagulant for the preparation of a concentrated PRP

Two APC programs are present on the IMPACT platform:

Concentration vs. whole blood1 Yield
Cell Types Platelets Leukocytes Erythrocytes Platelets
rACP (1 ml) >6 x 6 x <0,9 x 86%
wACP (1 ml) >4 x <0,5 x <0,03 x 74%

rAPC “Red” APC: Leukocyte-rich, erythrocyte-poor
wAPC “White” APC: Leukocyte-poor, erythrocyte-free

IMPACT APC is a highly concentrated platelet concentrate that has been optimised for maximum platelet yield. The final volume with which the evaluations were carried out is 1 ml of APC concentrate. The user has the possibility to vary the final volume himself.

ACS = AUTOLOGOUS CONDITIONED SERUM RICH IN ANTI-INFLAMMATORY CYTOKINES

ACS is a cell-free serum rich in signalling proteins such as growth factors and anti-inflammatory cytokines as well as exosomes.
The following diagram schematically shows the preparation protocol of ACS from the patient’s blood:

The following diagram schematically shows the production of ACS from the patient’s blood:

Step 1:

Step 2:

Step 3:

Composition of IMPACT ACS1

Oversupply of IL-1Ra versus IL-1ß
IL-1ß : IL-1Ra > 1 : 10

No significant increase of TNFa
TNFa (Whole blood) = TNFa (ACS)

IL-1Ra > 200pg/ml

Growth factors and cytokines like for example IL-10, IGF, PDGF

(1) Serum concentrations: TU Munich, Chair of Medical Technology

Extracellular Vesicles/ Exosomes in IMPACT ACS

A characterisation of EV markers in IMPACT ACS samples showed elevated concentrations of EVs/exosomes for CD9 and CD63 in ACS. The respective concentrations have been similar across samples, suggesting that most particles were both CD9 and CD63 positive. IMPACT ACS can therefore rightly be described as rich in regenerative exosomes.

A recent study by University for Continuing Education Krems, Faculty of Health and Medicine of 70 IMPACT ACS samples comprehensively characterized cytokine, growth factor, and degradative enzyme profiles in ACS derived from whole blood samples of OA patients compared to healthy individuals. Additionally, the potential impact of demographic and lifestyle-related factors was evaluated using a structured questionnaire, providing insights into patient-specific variability and its implications for ACS-based therapies. Publication submitted in May 2025.

STEM CELL PREPARATIONS

Stem Cell preparations are also considered autologous cell therapies.
Such cells can be obtained from fatty tissue or bone marrow, for example. These cell preparations contain so-called mesenchymal stem cells, which are also considered to play an important role in the regeneration of injured tissue.
Even though there is already initial experience in orthopaedics with such stem cell preparations, many questions such as optimal cell source, cell number, type of application (injection, carrier materials, etc.) or combination with growth factors are still unresolved.

Stem cells from bone marrow


Starting point:

Autologous bone marrow aspirate with anti-coagulant

Objective:
Yield of MSCs and MSC-like progenitor cells as well as platelets
Stem cells from fat tissue


Starting point:

Autologous fat tissue

Objective:
Yield of stromal vascular fraction (SVF) as well as the MSCs within SVF